1 Introduction


This project focuses on Analysis 2 of the Study Protocol, which aims to characterize pregnant individuals with OUD and examine hazards of maternal death and overdose. A poster was presented at Academy Health annual research meeting focusing on analysis on those with OUD and at least one day of MOUD prescription. (Section 7)

1.1 Methods


Data Source

  • TennCare data
  • TN all payer hospitalization database
  • Birth and death certificates
  • US Census data


Inclusion Criteria

  • Women 15-44 years old
  • Delivery of an infant >=20 weeks between 2007-2020
  • Continuous enrollment in TennCare from 90 pre-delivery through 41 days post partum
  • No sickle cell disease or active malignancy
  • With and without MOUD receipt initially, but only included those with MOUD for main analysis
  • Up to 5-days gap of continuous enrollment


  • Exposure: Days of MOUD supply between -90 days prior to delivery and +41 days post-delivery (maximum number of days = 132)
  • Covariates also collected during exposure period
  • Outcomes: first event of either overdose or death from 42 days post-delivery


Statistical analysis

Descriptive statistics were computed using frequencies (proportions) and medians (IQRs) as appropriate for the overall sample and also stratified by timing of MOUD receipt. Timing of MOUD receipt variable was categorized relative to timing of delivery and has two levels: receipt during one period only either pre- or post-delivery or receipt during both pre- and post-delivery periods. Due to the low number of outcomes, several variables were collapsed into one. These variables are listed below.


  • Route of delivery: Cesarean or Vaginal (Vaginal + Forcep + Vacuum)
  • Pain conditions: Back pain + dental pain + fibromyalgia + indicator for NSAIDs
  • Alcohol use disorder + other substance use
  • Benzodiazepine + Anticonvulsant use
  • Anxiety + Depression


Total days of MOUD receipt was calculated using three different methods. Method 1 sums the days supply variable (“daysup”) and if the pre-delivery period number is greater than 90 days, then it is capped at 90. Similarly, this method caps the post-delivery days supply to 42. Numerical example:

                           studyid from_day daysup total.rx.days
96  002007060499-05446655-02100650     -106     14            14
97  002007060499-05446655-02100650     -106     14            28
98  002007060499-05446655-02100650     -105     14            42
99  002007060499-05446655-02100650      -94     30            72
100 002007060499-05446655-02100650      -93     30            90
101 002007060499-05446655-02100650      -64      1            90
102 002007060499-05446655-02100650      -63     30            90

Pre-delivery days of MOUD is calculated as 90 for this individual.


Method 2 also sums the days supply variable, but the number of days over 90 is added to the post-delivery period. Method 2 caps the pre-delivery days to 90 and the post delivery days to 42. Numerical example below:

                           studyid from_day daysup total.rx.days
96  002007060499-05446655-02100650     -106     14            14
97  002007060499-05446655-02100650     -106     14            28
98  002007060499-05446655-02100650     -105     14            42
99  002007060499-05446655-02100650      -94     30            72
100 002007060499-05446655-02100650      -93     30           102
101 002007060499-05446655-02100650      -64      1           103
102 002007060499-05446655-02100650      -63     30           133

Pre-delivery days of MOUD is calculated as 90 for this individual, and the additional 43 days are carried over to the post-delivery period. However, the post-delivery days supply is capped to 42.


Method 3 was used in the conference abstract, as it was the most conservative approach. This method counts for overlapping prescription dates using the “from_day” variable, which is the number of days anchored from Day 42 of the exposure period (e.g. from_day -132 is the first day of the exposure period), and sums the number of days covered. Days supply greater than 90 in the pre-period is carried onto the post-delivery period but overlapping prescription dates are not counted. Numerical example below:


                           studyid daysup from_day
96  002007060499-05446655-02100650     14     -106
97  002007060499-05446655-02100650     14     -106
98  002007060499-05446655-02100650     14     -105
99  002007060499-05446655-02100650     30      -94
100 002007060499-05446655-02100650     30      -93
101 002007060499-05446655-02100650      1      -64
102 002007060499-05446655-02100650     30      -63
                          studyid pre_days_covered carryover_days
17 002007060499-05446655-02100650               64              9


For this individual, 64 days are counted starting from Day -106 to -43 days and 9 carryover days are counted into the post-delivery period.


After calculating the number of days of MOUD receipt, various histograms were plotted to examine differences by method. Then, multivariable Cox Proportional hazards model were used to determine the associations between total days of MOUD receipt as the main exposure and death or overdose as the outcome. For individuals with multiple outcomes, the earliest outcome was used. Outcomes that occurred during the follow-up period were counted if they were captured in the TN all payer database if an individual lost eligibility for TennCare. Average dose per day of MOUD receipt (qty*dose)/(days supply) was also calculated and described in the table. Average days supply and dose from the pre-delivery period that exceeded 90 days was carried over and added to the post-delivery period.


The Cox model was first modeled using linear continuous terms, due to the limited degrees of freedom. However, year of delivery was determined to be non-linear and was modeled using a restricted cubic spline with 3 knots. These models included the following covariates: year of delivery, total day MOUD receipt, age at delivery, gestation weeks, route of delivery, combined pain conditions, alcohol/other substance use, benzodiazepine/anticonvulsant use, anxiety/depression, maternal morbidity (CDC defined). Additional covariates were included initially but were removed due to the small number of outcomes. These include race/ethnicity combined, number of previous pregnancies, schizophrenia/personality disorder, CDC social vulnerability index, and timing of MOUD receipt (one or two periods relative to delivery). Robust standard errors clustered at the individual level were computed.


Future analyses planned: + Repeat analysis excluding those who received naltrexone and methadone + Include individuals with the exposure period starting at 180 days before delivery + Include individuals with up to 30-days gap in enrollment


Additonal notes: few outcomes (<5) prior to 2015


2 Descriptive Statistics (90 days pre-delivery & up to 5 days loss enroll)

2.1 Demographics/Clinical Characteristics

2.1.1 Column percents


  • There are 15103 pregnancies in 12532 unique individuals
N No MOUD MOUD Test Statistic
(N=7631) (N=7472)
Year of delivery 15103 (100.00) F1,15101=1238.74, P<0.00013
        Median (interquartile range) 2014 (2011—2017) 2016 (2014—2018)
        Range 2007—2020 2007—2020
Age at delivery 15103 (100.00) F1,15101=79.02, P<0.00013
        Median (interquartile range) 27 (23—30) 27 (24—31)
        Range 15—44 17—44
Number of Gestation weeks 15103 (100.00) F1,15101=97.93, P<0.00013
        Median (interquartile range) 38 (37—39) 39 (37—39)
        Range 22—43 21—42
Race 15099 (99.97) Χ2
4
=212.83, P<0.00012
        American Indian or Alaska Native     21/7627 (0.28)     23/7472 (0.31)
        Asian or Pacific Islander     14/7627 (0.18)     11/7472 (0.15)
        Black of African American     617/7627 (8.09)     210/7472 (2.81)
        Other or Unknown     86/7627 (1.13)     53/7472 (0.71)
        White 6889/7627 (90.32) 7175/7472 (96.03)
Hispanic : Not Hispanic 15089 (99.91) 7534/7624 (98.82) 7398/7465 (99.10) Χ2
1
=2.93, P=0.08682
Race/Ethnicity combined 15103 (100.00) Χ2
4
=209.22, P<0.00012
        Hispanic     90/7631 (1.18)     67/7472 (0.90)
        Non-Hispanic Asian     13/7631 (0.17)     11/7472 (0.15)
        Non-Hispanic Black     613/7631 (8.03)     209/7472 (2.80)
        Non-Hispanic Other     74/7631 (0.97)     55/7472 (0.74)
        Non-Hispanic White 6841/7631 (89.65) 7130/7472 (95.42)
Route of delivery : Vaginal 15103 (100.00) 4966/7631 (65.08) 4857/7472 (65.00) Χ2
1
=0.01, P=0.92412
Number of previous pregnancies 14869 (98.45) F1,14867=6.63, P=0.01003
        Median (interquartile range) 2 (1—3) 2 (1—3)
        Range 0—24 0—23
Final outcome 15103 (100.00) Χ2
3
=411.87, P<0.00012
        Death     47/7631 (0.62)     30/7472 (0.40)
        Overdose     84/7631 (1.10)     97/7472 (1.30)
        Loss of enrollment 1629/7631 (21.35)     709/7472 (9.49)
        Censored 5871/7631 (76.94) 6636/7472 (88.81)
Final outcome (w/o all payer data) 15103 (100.00) Χ2
3
=409.14, P<0.00012
        Death     19/7631 (0.25)     11/7472 (0.15)
        Overdose     77/7631 (1.01)     91/7472 (1.22)
        Loss of enrollment 1664/7631 (21.81)     734/7472 (9.82)
        Censored 5871/7631 (76.94) 6636/7472 (88.81)
Total days supplied MOUD 15103 (100.00) F1,15101=93419.74, P<0.00013
        Median (interquartile range) 0 (0—0) 96 (56—120)
        Range 0—112 1—132
Total days supplied MOUD before delivery 15103 (100.00) F1,15101=46301.24, P<0.00013
        Median (interquartile range) 0 (0—0) 74 (35—90)
        Range 0—84 0—90
Total days supplied MOUD after delivery 15103 (100.00) F1,15101=24424.08, P<0.00013
        Median (interquartile range) 0 (0—0) 30 (9—42)
        Range 0—28 0—42
Total days supplied MOUD (method 2) 15103 (100.00) F1,15101=93814.73, P<0.00013
        Median (interquartile range) 0 (0—0) 98 (56—125)
        Range 0—112 1—132
Total days supplied MOUD before delivery (method 2) 15103 (100.00) F1,15101=46301.24, P<0.00013
        Median (interquartile range) 0 (0—0) 74 (35—90)
        Range 0—84 0—90
Total days supplied MOUD after delivery (method 2) 15103 (100.00) F1,15101=27941.69, P<0.00013
        Median (interquartile range) 0 (0—0) 30 (14—42)
        Range 0—28 0—42
Total days supplied MOUD (method 3) 7472 (49.47)
        Median (interquartile range) 89 (47—112)
        Range 1—132
Total days supplied MOUD before delivery (method 3) 7472 (49.47)
        Median (interquartile range) 62 (30—78)
        Range 0—90
Total days supplied MOUD after delivery (method 3) 7472 (49.47)
        Median (interquartile range) 30 (13—40)
        Range 0—42
Avg dose pre-delivery (mg) 7394 (48.96)
        Median (interquartile range) 14.24 (8.00—16.00)
        Range 0.00—50.00
Avg dose post-delivery (mg) 7394 (48.96)
        Median (interquartile range) 9.72 (4.00—16.00)
        Range 0.00—53.57
Avg dose exposure (mg) 7394 (48.96)
        Median (interquartile range) 14.09 (9.42—16.00)
        Range 0.14—53.57
Total days buprenorphine before delivery (method 3) 7299 (48.33)
        Median (interquartile range) 63.00 (30.00—78.00)
        Range 0.00—90.00
Total days buprenorphine after delivery (method 3) 7299 (48.33)
        Median (interquartile range) 30.00 (13.00—41.00)
        Range 0.00—42.00
Total days supplied buprenorphine 7299 (48.33)
        Median (interquartile range) 90.00 (49.00—112.00)
        Range 1.00—132.00
Avg dose BUP pre-delivery (mg) 7298 (48.32)
        Median (interquartile range) 14.12 (8.00—16.00)
        Range 0.00—35.42
Avg dose BUP post-delivery (mg) 7298 (48.32)
        Median (interquartile range) 9.71 (4.00—16.00)
        Range 0.00—42.67
Avg dose BUP exposure (mg) 7298 (48.32)
        Median (interquartile range) 13.98 (9.13—16.00)
        Range 0.14—42.67
Combined pain : Yes 15103 (100.00) 6000/7631 (78.63) 5766/7472 (77.17) Χ2
1
=4.67, P=0.03082
Schizophrenia or personality disorder : Yes 15103 (100.00)     598/7631 (7.84)     583/7472 (7.80) Χ2
1
=0.01, P=0.93802
Alcohol or other substance use : Yes 15103 (100.00) 4490/7631 (58.84) 3342/7472 (44.73) Χ2
1
=301.15, P<0.00012
Benzodiazepine or anticonvulsant use : Yes 15103 (100.00)     996/7631 (13.05) 1077/7472 (14.41) Χ2
1
=5.91, P=0.01502
Maternal morbidity : Yes 15103 (100.00)     776/7631 (10.17)     528/7472 (7.07) Χ2
1
=46.07, P<0.00012
Anxiety and depression combined : Yes 15103 (100.00) 2987/7631 (39.14) 3485/7472 (46.64) Χ2
1
=86.67, P<0.00012
Back pain : Yes 15103 (100.00) 3189/7631 (41.79) 2528/7472 (33.83) Χ2
1
=101.61, P<0.00012
Depression : Yes 15103 (100.00) 2587/7631 (33.90) 2946/7472 (39.43) Χ2
1
=49.66, P<0.00012
Bipolar disorder : Yes 15103 (100.00)     830/7631 (10.88)     819/7472 (10.96) Χ2
1
=0.03, P=0.86822
Other substance use : Yes 15103 (100.00) 4363/7631 (57.17) 3197/7472 (42.79) Χ2
1
=312.63, P<0.00012
Tobacco use : Yes 15103 (100.00) 5201/7631 (68.16) 5196/7472 (69.54) Χ2
1
=3.37, P=0.06652
Med NSAIDS : Yes 15103 (100.00) 4754/7631 (62.30) 4602/7472 (61.59) Χ2
1
=0.80, P=0.36992
Schizophrenia psychotic disorders : Yes 15103 (100.00)     398/7631 (5.22)     466/7472 (6.24) Χ2
1
=7.30, P=0.00692
Anxiety : Yes 15103 (100.00) 1113/7631 (14.59) 1608/7472 (21.52) Χ2
1
=122.93, P<0.00012
Med benzodiazepine use : Yes 15103 (100.00)     660/7631 (8.65)     713/7472 (9.54) Χ2
1
=3.65, P=0.05622
Maternal morbidity : Yes 15103 (100.00)     776/7631 (10.17)     528/7472 (7.07) Χ2
1
=46.07, P<0.00012
Dental pain : Yes 15103 (100.00)     410/7631 (5.37)     298/7472 (3.99) Χ2
1
=16.20, P=0.00012
Alcohol use disorder : Yes 15103 (100.00)     502/7631 (6.58)     507/7472 (6.79) Χ2
1
=0.26, P=0.61062
Med anticonvulsant use : Yes 15103 (100.00)     423/7631 (5.54)     432/7472 (5.78) Χ2
1
=0.40, P=0.52622
Med muscle relaxant use : Yes 15103 (100.00)     649/7631 (8.50)     371/7472 (4.97) Χ2
1
=75.11, P<0.00012
Personality disorder : Yes 15103 (100.00)     283/7631 (3.71)     220/7472 (2.94) Χ2
1
=6.85, P=0.00892
Fibromyalgia : Yes 15103 (100.00)     555/7631 (7.27)     383/7472 (5.13) Χ2
1
=29.88, P<0.00012
CDC SVI overall percentile ranking of all 4 themes 14003 (92.72) F1,14001=18.02, P<0.00013
        Median (interquartile range) 0.60 (0.38—0.81) 0.58 (0.37—0.79)
        Range 0.00—1.00 0.00—1.00
N is the number of non-missing value. 1Kruskal-Wallis. 2Pearson. 3Wilcoxon.


  • Outlier with average dose of 16,000 due to quantity of (56,000 * 8mg)/28 days

2.1.2 Characteristics based on MOUD timing (method 3)

N No MOUD Only pre Only post Both pre and post
(N=7631) (N=898) (N=638) (N=5936)
Year of delivery 15103 (100.00)
        Median (interquartile range) 2014 (2011—2017) 2016 (2015—2018) 2016 (2014—2019) 2016 (2014—2018)
        Range 2007—2020 2007—2020 2007—2020 2007—2020
Year of delivery as categorical 15103 (100.00)
        2007     284/7631 (3.72)     1/898 (0.11)     6/638 (0.94)     25/5936 (0.42)
        2008     312/7631 (4.09)     3/898 (0.33)     15/638 (2.35)     41/5936 (0.69)
        2009     467/7631 (6.12)     10/898 (1.11)     19/638 (2.98)     52/5936 (0.88)
        2010     478/7631 (6.26)     6/898 (0.67)     24/638 (3.76)     112/5936 (1.89)
        2011     554/7631 (7.26)     19/898 (2.12)     27/638 (4.23)     146/5936 (2.46)
        2012     611/7631 (8.01)     28/898 (3.12)     19/638 (2.98)     223/5936 (3.76)
        2013     595/7631 (7.80)     40/898 (4.45)     43/638 (6.74)     438/5936 (7.38)
        2014     659/7631 (8.64)     79/898 (8.80)     48/638 (7.52)     684/5936 (11.52)
        2015     690/7631 (9.04) 121/898 (13.47)     60/638 (9.40)     821/5936 (13.83)
        2016     769/7631 (10.08) 155/898 (17.26)     61/638 (9.56)     769/5936 (12.95)
        2017     667/7631 (8.74) 124/898 (13.81)     70/638 (10.97)     635/5936 (10.70)
        2018     610/7631 (7.99) 125/898 (13.92)     58/638 (9.09)     621/5936 (10.46)
        2019     552/7631 (7.23) 113/898 (12.58)     91/638 (14.26)     663/5936 (11.17)
        2020     383/7631 (5.02)     74/898 (8.24)     97/638 (15.20)     706/5936 (11.89)
Age at delivery 15103 (100.00)
        Median (interquartile range) 27 (23—30) 27 (24—31) 27 (24—31) 27 (24—31)
        Range 15—44 18—43 17—44 17—44
Number of Gestation weeks 15103 (100.00)
        Median (interquartile range) 38 (37—39) 39 (37—39) 38 (37—39) 39 (37—39)
        Range 22—43 24—42 23—42 21—42
Race 15099 (99.97)
        American Indian or Alaska Native     21/7627 (0.28)     4/898 (0.45)     3/638 (0.47)     16/5936 (0.27)
        Asian or Pacific Islander     14/7627 (0.18)     1/898 (0.11)     1/638 (0.16)         9/5936 (0.15)
        Black of African American     617/7627 (8.09)     35/898 (3.90)     22/638 (3.45)     153/5936 (2.58)
        Other or Unknown     86/7627 (1.13)     11/898 (1.22)     5/638 (0.78)     37/5936 (0.62)
        White 6889/7627 (90.32) 847/898 (94.32) 607/638 (95.14) 5721/5936 (96.38)
Hispanic : Not Hispanic 15089 (99.91) 7534/7624 (98.82) 886/895 (98.99) 633/637 (99.37) 5879/5933 (99.09)
Race/Ethnicity combined 15103 (100.00)
        Hispanic     90/7631 (1.18)     9/898 (1.00)     4/638 (0.63)     54/5936 (0.91)
        Non-Hispanic Asian     13/7631 (0.17)     1/898 (0.11)     1/638 (0.16)         9/5936 (0.15)
        Non-Hispanic Black     613/7631 (8.03)     34/898 (3.79)     22/638 (3.45)     153/5936 (2.58)
        Non-Hispanic Other     74/7631 (0.97)     13/898 (1.45)     7/638 (1.10)     35/5936 (0.59)
        Non-Hispanic White 6841/7631 (89.65) 841/898 (93.65) 604/638 (94.67) 5685/5936 (95.77)
Route of delivery : Vaginal 15103 (100.00) 4966/7631 (65.08) 614/898 (68.37) 421/638 (65.99) 3822/5936 (64.39)
Number of previous pregnancies 14869 (98.45)
        Median (interquartile range) 2 (1—3) 2 (1—3) 2 (1—3) 2 (1—3)
        Range 0—24 0—19 0—23 0—23
Final outcome 15103 (100.00)
        Death     47/7631 (0.62)     3/898 (0.33)     2/638 (0.31)     25/5936 (0.42)
        Overdose     84/7631 (1.10)     19/898 (2.12)     16/638 (2.51)     62/5936 (1.04)
        Loss of enrollment 1629/7631 (21.35) 100/898 (11.14)     90/638 (14.11)     519/5936 (8.74)
        Censored 5871/7631 (76.94) 776/898 (86.41) 530/638 (83.07) 5330/5936 (89.79)
Total days supplied MOUD 15103 (100.00)
        Median (interquartile range) 0 (0—0) 30 (15—56) 28 (14—33) 108 (84—122)
        Range 0—112 1—90 1—70 7—132
Total days supplied MOUD before delivery 15103 (100.00)
        Median (interquartile range) 0 (0—0) 30 (15—56) 0 (0—0) 84 (60—90)
        Range 0—84 1—90 0—28 1—90
Total days supplied MOUD after delivery 15103 (100.00)
        Median (interquartile range) 0 (0—0) 0 (0—0) 28 (14—33) 30 (21—42)
        Range 0—28 0—0 1—42 0—42
Total days supplied MOUD (method 2) 15103 (100.00)
        Median (interquartile range) 0 (0—0) 30 (15—56) 28 (14—33) 112 (84—129)
        Range 0—112 1—132 1—70 7—132
Total days supplied MOUD before delivery (method 2) 15103 (100.00)
        Median (interquartile range) 0 (0—0) 30 (15—56) 0 (0—0) 84 (60—90)
        Range 0—84 1—90 0—28 1—90
Total days supplied MOUD after delivery (method 2) 15103 (100.00)
        Median (interquartile range) 0 (0—0) 0 (0—0) 28 (14—33) 35 (24—42)
        Range 0—28 0—42 1—42 0—42
Total days supplied MOUD (method 3) 7472 (49.47)
        Median (interquartile range) 30 (14—49) 14 (7—25) 100 (76—116)
        Range 1—89 1—41 7—132
Total days supplied MOUD before delivery (method 3) 7472 (49.47)
        Median (interquartile range) 30 (14—49) 0 (0—0) 69 (48—80)
        Range 1—89 0—0 1—90
Total days supplied MOUD after delivery (method 3) 7472 (49.47)
        Median (interquartile range) 0 (0—0) 14 (7—25) 35 (23—41)
        Range 0—0 1—41 1—42
Avg dose pre-delivery (mg) 7394 (48.96)
        Median (interquartile range) 13.90 (8.00—16.00) 0.00 (0.00—0.00) 15.00 (9.94—16.00)
        Range 0.14—50.00 0.00—0.00 0.25—50.00
Avg dose post-delivery (mg) 7394 (48.96)
        Median (interquartile range) 0.00 (0.00—0.00) 15.76 (8.12—16.00) 12.00 (8.00—16.00)
        Range 0.00—0.00 0.80—53.57 0.00—50.00
Avg dose exposure (mg) 7394 (48.96)
        Median (interquartile range) 13.90 (8.00—16.00) 15.76 (8.12—16.00) 14.04 (9.87—16.00)
        Range 0.14—50.00 0.80—53.57 0.25—50.00
Total days buprenorphine before delivery (method 3) 7299 (48.33)
        Median (interquartile range) 30.00 (14.00—49.00) 0.00 (0.00—0.00) 69.00 (48.00—80.00)
        Range 1.00—89.00 0.00—0.00 0.00—90.00
Total days buprenorphine after delivery (method 3) 7299 (48.33)
        Median (interquartile range) 0.00 (0.00—0.00) 14.50 (7.00—25.00) 35.00 (23.00—41.00)
        Range 0.00—0.00 1.00—41.00 0.00—42.00
Total days supplied buprenorphine 7299 (48.33)
        Median (interquartile range) 30.00 (14.00—49.00) 14.50 (7.00—25.00) 100.00 (76.00—116.00)
        Range 1.00—89.00 1.00—41.00 4.00—132.00
Avg dose BUP pre-delivery (mg) 7298 (48.32)
        Median (interquartile range) 13.33 (8.00—16.00) 0.00 (0.00—0.00) 14.86 (9.67—16.00)
        Range 0.14—29.71 0.00—0.00 0.00—35.42
Avg dose BUP post-delivery (mg) 7298 (48.32)
        Median (interquartile range) 0.00 (0.00—0.00) 15.30 (8.00—16.00) 12.00 (8.00—16.00)
        Range 0.00—0.00 0.80—42.67 0.00—33.24
Avg dose BUP exposure (mg) 7298 (48.32)
        Median (interquartile range) 13.33 (8.00—16.00) 15.30 (8.00—16.00) 13.98 (9.75—16.00)
        Range 0.14—29.71 0.80—42.67 0.25—34.47
Combined pain : Yes 15103 (100.00) 6000/7631 (78.63) 702/898 (78.17) 473/638 (74.14) 4591/5936 (77.34)
Schizophrenia or personality disorder : Yes 15103 (100.00)     598/7631 (7.84)     83/898 (9.24)     66/638 (10.34)     434/5936 (7.31)
Alcohol or other substance use : Yes 15103 (100.00) 4490/7631 (58.84) 441/898 (49.11) 315/638 (49.37) 2586/5936 (43.56)
Benzodiazepine or anticonvulsant use : Yes 15103 (100.00)     996/7631 (13.05) 131/898 (14.59)     87/638 (13.64)     859/5936 (14.47)
Maternal morbidity : Yes 15103 (100.00)     776/7631 (10.17)     69/898 (7.68)     52/638 (8.15)     407/5936 (6.86)
Anxiety and depression combined : Yes 15103 (100.00) 2987/7631 (39.14) 403/898 (44.88) 337/638 (52.82) 2745/5936 (46.24)
Back pain : Yes 15103 (100.00) 3189/7631 (41.79) 308/898 (34.30) 190/638 (29.78) 2030/5936 (34.20)
Depression : Yes 15103 (100.00) 2587/7631 (33.90) 338/898 (37.64) 294/638 (46.08) 2314/5936 (38.98)
Bipolar disorder : Yes 15103 (100.00)     830/7631 (10.88) 110/898 (12.25)     61/638 (9.56)     648/5936 (10.92)
Other substance use : Yes 15103 (100.00) 4363/7631 (57.17) 434/898 (48.33) 303/638 (47.49) 2460/5936 (41.44)
Tobacco use : Yes 15103 (100.00) 5201/7631 (68.16) 651/898 (72.49) 428/638 (67.08) 4117/5936 (69.36)
Med NSAIDS : Yes 15103 (100.00) 4754/7631 (62.30) 551/898 (61.36) 384/638 (60.19) 3667/5936 (61.78)
Schizophrenia psychotic disorders : Yes 15103 (100.00)     398/7631 (5.22)     64/898 (7.13)     49/638 (7.68)     353/5936 (5.95)
Anxiety : Yes 15103 (100.00) 1113/7631 (14.59) 208/898 (23.16) 140/638 (21.94) 1260/5936 (21.23)
Med benzodiazepine use : Yes 15103 (100.00)     660/7631 (8.65)     93/898 (10.36)     56/638 (8.78)     564/5936 (9.50)
Maternal morbidity : Yes 15103 (100.00)     776/7631 (10.17)     69/898 (7.68)     52/638 (8.15)     407/5936 (6.86)
Dental pain : Yes 15103 (100.00)     410/7631 (5.37)     44/898 (4.90)     30/638 (4.70)     224/5936 (3.77)
Alcohol use disorder : Yes 15103 (100.00)     502/7631 (6.58)     66/898 (7.35)     64/638 (10.03)     377/5936 (6.35)
Med anticonvulsant use : Yes 15103 (100.00)     423/7631 (5.54)     48/898 (5.35)     33/638 (5.17)     351/5936 (5.91)
Med muscle relaxant use : Yes 15103 (100.00)     649/7631 (8.50)     57/898 (6.35)     50/638 (7.84)     264/5936 (4.45)
Personality disorder : Yes 15103 (100.00)     283/7631 (3.71)     35/898 (3.90)     31/638 (4.86)     154/5936 (2.59)
Fibromyalgia : Yes 15103 (100.00)     555/7631 (7.27)     55/898 (6.12)     29/638 (4.55)     299/5936 (5.04)
CDC SVI overall percentile ranking of all 4 themes 14003 (92.72)
        Median (interquartile range) 0.60 (0.38—0.81) 0.61 (0.38—0.81) 0.58 (0.37—0.78) 0.57 (0.36—0.78)
        Range 0.00—1.00 0.00—1.00 0.00—1.00 0.00—1.00
N is the number of non-missing value. 1Kruskal-Wallis. 2Pearson. 3Wilcoxon.


2.2 Histogram of MOUD days supplied

2.2.1 Before delivery up to 90 days (Method 1)

2.2.2 Before delivery up to 90 days (Method 2)


2.2.3 Before delivery up to 90 days (Method 3)


2.2.4 After delivery up to 41 days (Method 1)

2.2.5 After delivery up to 41 days (Method 2)


2.2.6 After delivery up to 41 days (Method 3)


2.2.7 Entire exposure (Method 1)


2.2.8 Entire exposure (Method 2)


2.2.9 Entire exposure (Method 3)


2.2.10 Entire exposure buprenorphine only (Method 3)


3 Survival Analysis

3.1 Kaplan Meier Plot by MOUD


3.2 Log-Rank Test

Call:
survdiff(formula = Surv(days.to.event, outcome.bin) ~ moud.yes, 
    data = basic)

              N Observed Expected (O-E)^2/E (O-E)^2/V
moud.yes=0 7631      131      130   0.00421   0.00851
moud.yes=1 7472      127      128   0.00430   0.00851

 Chisq= 0  on 1 degrees of freedom, p= 0.9 
  • There is a statistically significant difference in death or overdose between the two groups


3.3 Multivariable Cox PH model

3.3.1 Linear continuous terms

Effects   Response: Surv(days.to.event, outcome.bin)
Low High Δ Effect S.E. Lower 0.95 Upper 0.95
Year of delivery 2000.00 2000.00 2.0 0.380 0.100 0.180 0.580
Hazard Ratio 2000.00 2000.00 2.0 1.500 1.200 1.800
Total days supplied MOUD (method 3) 1.00 31.00 30.0 -0.170 0.066 -0.300 -0.039
Hazard Ratio 1.00 31.00 30.0 0.850 0.740 0.960
Age at delivery 27.00 31.00 4.0 -0.120 0.084 -0.280 0.049
Hazard Ratio 27.00 31.00 4.0 0.890 0.760 1.000
Number of Gestation weeks 37.00 39.00 2.0 -0.094 0.072 -0.230 0.048
Hazard Ratio 37.00 39.00 2.0 0.910 0.790 1.000
CDC SVI overall percentile ranking of all 4 themes 0.25 0.75 0.5 -0.240 0.190 -0.620 0.140
Hazard Ratio 0.25 0.75 0.5 0.790 0.540 1.100
Number of previous pregnancies 1.00 3.00 2.0 0.034 0.097 -0.160 0.220
Hazard Ratio 1.00 3.00 2.0 1.000 0.860 1.300
Race/Ethnicity binary --- All Other:Non---Hispanic White 2.00 1.00 0.700 0.310 0.093 1.300
Hazard Ratio 2.00 1.00 2.000 1.100 3.700
Route of delivery --- Cesarean:Vaginal 2.00 1.00 0.014 0.200 -0.380 0.410
Hazard Ratio 2.00 1.00 1.000 0.690 1.500
Combined pain --- Yes:No 1.00 2.00 -0.340 0.200 -0.740 0.056
Hazard Ratio 1.00 2.00 0.710 0.480 1.100
Schizophrenia or personality disorder --- Yes:No 1.00 2.00 0.340 0.260 -0.180 0.860
Hazard Ratio 1.00 2.00 1.400 0.840 2.400
Alcohol or other substance use --- Yes:No 1.00 2.00 0.260 0.200 -0.130 0.640
Hazard Ratio 1.00 2.00 1.300 0.880 1.900
Benzodiazepine or anticonvulsant use --- Yes:No 1.00 2.00 0.170 0.240 -0.310 0.640
Hazard Ratio 1.00 2.00 1.200 0.730 1.900
Anxiety --- Yes:No 1.00 2.00 0.260 0.210 -0.150 0.660
Hazard Ratio 1.00 2.00 1.300 0.860 1.900
Depression --- Yes:No 1.00 2.00 0.570 0.200 0.180 0.960
Hazard Ratio 1.00 2.00 1.800 1.200 2.600
Maternal morbidity --- Yes:No 1.00 2.00 -0.075 0.400 -0.860 0.710
Hazard Ratio 1.00 2.00 0.930 0.420 2.000
Wald Statistics for Surv(days.to.event, outcome.bin)
χ2 d.f. P
Year of delivery 13.56 1 0.0002
Total days supplied MOUD (method 3) 6.47 1 0.0110
Age at delivery 1.91 1 0.1670
Race/Ethnicity binary 5.12 1 0.0236
Route of delivery 0.01 1 0.9426
Number of Gestation weeks 1.68 1 0.1945
Combined pain 2.84 1 0.0918
Schizophrenia or personality disorder 1.67 1 0.1966
Alcohol or other substance use 1.74 1 0.1875
Benzodiazepine or anticonvulsant use 0.47 1 0.4942
Anxiety 1.57 1 0.2105
Depression 8.33 1 0.0039
Maternal morbidity 0.04 1 0.8506
CDC SVI overall percentile ranking of all 4 themes 1.58 1 0.2092
Number of previous pregnancies 0.12 1 0.7252
TOTAL 80.25 15 <0.0001


3.3.2 With splines

Effects   Response: Surv(days.to.event, outcome.bin)
Low High Δ Effect S.E. Lower 0.95 Upper 0.95
Year of delivery 2016.00 2018.00 2.0 0.47090 0.11120 0.25290 0.68880
Hazard Ratio 2016.00 2018.00 2.0 1.60100 1.28800 1.99100
Total days supplied MOUD (method 3) 1.00 31.00 30.0 0.01435 0.17160 -0.32200 0.35070
Hazard Ratio 1.00 31.00 30.0 1.01400 0.72470 1.42000
Age at delivery 27.00 31.00 4.0 -0.11630 0.08410 -0.28120 0.04851
Hazard Ratio 27.00 31.00 4.0 0.89020 0.75490 1.05000
Number of Gestation weeks 39.00 37.00 -2.0 0.09535 0.07286 -0.04745 0.23810
Hazard Ratio 39.00 37.00 -2.0 1.10000 0.95370 1.26900
CDC SVI overall percentile ranking of all 4 themes 0.25 0.75 0.5 -0.23650 0.19350 -0.61580 0.14280
Hazard Ratio 0.25 0.75 0.5 0.78940 0.54020 1.15400
Number of previous pregnancies 1.00 3.00 2.0 0.03295 0.09814 -0.15940 0.22530
Hazard Ratio 1.00 3.00 2.0 1.03300 0.85270 1.25300
Race/Ethnicity binary --- All Other:Non---Hispanic White 2.00 1.00 0.68920 0.31030 0.08100 1.29700
Hazard Ratio 2.00 1.00 1.99200 1.08400 3.66000
Route of delivery --- Cesarean:Vaginal 2.00 1.00 0.02069 0.20030 -0.37190 0.41330
Hazard Ratio 2.00 1.00 1.02100 0.68940 1.51200
Combined pain --- Yes:No 1.00 2.00 -0.35180 0.20420 -0.75190 0.04833
Hazard Ratio 1.00 2.00 0.70340 0.47150 1.05000
Schizophrenia or personality disorder --- Yes:No 1.00 2.00 0.31730 0.26290 -0.19800 0.83250
Hazard Ratio 1.00 2.00 1.37300 0.82040 2.29900
Alcohol or other substance use --- Yes:No 1.00 2.00 0.25230 0.19610 -0.13190 0.63660
Hazard Ratio 1.00 2.00 1.28700 0.87640 1.89000
Benzodiazepine or anticonvulsant use --- Yes:No 1.00 2.00 0.18050 0.24620 -0.30210 0.66320
Hazard Ratio 1.00 2.00 1.19800 0.73930 1.94100
Anxiety --- Yes:No 1.00 2.00 0.26620 0.20840 -0.14220 0.67460
Hazard Ratio 1.00 2.00 1.30500 0.86740 1.96300
Depression --- Yes:No 1.00 2.00 0.56730 0.19880 0.17780 0.95690
Hazard Ratio 1.00 2.00 1.76400 1.19500 2.60400
Maternal morbidity --- Yes:No 1.00 2.00 -0.08026 0.39990 -0.86400 0.70350
Hazard Ratio 1.00 2.00 0.92290 0.42150 2.02100
Wald Statistics for Surv(days.to.event, outcome.bin)
χ2 d.f. P
Year of delivery 20.30 2 <0.0001
Nonlinear 1.58 1 0.2082
Total days supplied MOUD (method 3) 6.82 2 0.0331
Nonlinear 1.34 1 0.2472
Age at delivery 1.92 1 0.1663
Race/Ethnicity binary 4.94 1 0.0262
Route of delivery 0.01 1 0.9177
Number of Gestation weeks 1.72 1 0.1902
Combined pain 2.97 1 0.0849
Schizophrenia or personality disorder 1.46 1 0.2269
Alcohol or other substance use 1.66 1 0.1979
Benzodiazepine or anticonvulsant use 0.54 1 0.4634
Anxiety 1.63 1 0.2013
Depression 8.15 1 0.0043
Maternal morbidity 0.04 1 0.8408
CDC SVI overall percentile ranking of all 4 themes 1.49 1 0.2215
Number of previous pregnancies 0.11 1 0.7368
TOTAL NONLINEAR 3.02 2 0.2207
TOTAL 90.75 17 <0.0001


4 Propensity Score (Matching Weights) by MOUD receipt


  • Mirror histograms show propensity scores of the control group above the horizontal line in white, while the treatment group is below the horizontal line in dark green. Light green bars display the summation of weights of subjects within each propensity score stratum. This plot shows good overlap between the control and treatment groups, and the close similarity between them after applying matching weights.

4.1 Absolute standardized mean difference plot


4.2 Logistic regression model


Call:
glm(formula = outcome.bin ~ moud.yes, family = binomial(link = "logit"), 
    data = basic, weights = mw$W)

Coefficients:
            Estimate Std. Error z value            Pr(>|z|)    
(Intercept)  -3.9566     0.1009 -39.221 <0.0000000000000002 ***
moud.yes     -0.2424     0.1508  -1.608               0.108    
---
Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1

(Dispersion parameter for binomial family taken to be 1)

    Null deviance: 1838.6  on 15102  degrees of freedom
Residual deviance: 1836.0  on 15101  degrees of freedom
AIC: 1772.4

Number of Fisher Scoring iterations: 7


  • exponentiated Odds Ratio
                    OR      2.5 %     97.5 %
(Intercept) 0.01912766 0.01559458 0.02316825
moud.yes    0.78472227 0.58274573 1.05351362


5 Only including data of women with MOUD receipt

5.1 Descriptive Statistics


  • There are 7472 pregnancies in 6387 unique individuals
    N Overall
    (N=7472)
    Year of delivery 7472 (100.00)
            Median (interquartile range) 2016 (2014—2018)
            Range 2007—2020
    Age at delivery 7472 (100.00)
            Median (interquartile range) 27 (24—31)
            Range 17—44
    Number of Gestation weeks 7472 (100.00)
            Median (interquartile range) 39 (37—39)
            Range 21—42
    Race 7472 (100.00)
            American Indian or Alaska Native     23/7472 (0.31)
            Asian or Pacific Islander     11/7472 (0.15)
            Black of African American     210/7472 (2.81)
            Other or Unknown     53/7472 (0.71)
            White 7175/7472 (96.03)
    Hispanic : Not Hispanic 7465 (99.91) 7398/7465 (99.10)
    Race/Ethnicity combined 7472 (100.00)
            Hispanic     67/7472 (0.90)
            Non-Hispanic Asian     11/7472 (0.15)
            Non-Hispanic Black     209/7472 (2.80)
            Non-Hispanic Other     55/7472 (0.74)
            Non-Hispanic White 7130/7472 (95.42)
    Route of delivery : Vaginal 7472 (100.00) 4857/7472 (65.00)
    Number of previous pregnancies 7335 (98.17)
            Median (interquartile range) 2 (1—3)
            Range 0—23
    Final outcome 7472 (100.00)
            Death     30/7472 (0.40)
            Overdose     97/7472 (1.30)
            Loss of enrollment     709/7472 (9.49)
            Censored 6636/7472 (88.81)
    Final outcome (w/o all payer data) 7472 (100.00)
            Death     11/7472 (0.15)
            Overdose     91/7472 (1.22)
            Loss of enrollment     734/7472 (9.82)
            Censored 6636/7472 (88.81)
    Total days supplied MOUD 7472 (100.00)
            Median (interquartile range) 96 (56—120)
            Range 1—132
    Total days supplied MOUD before delivery 7472 (100.00)
            Median (interquartile range) 74 (35—90)
            Range 0—90
    Total days supplied MOUD after delivery 7472 (100.00)
            Median (interquartile range) 30 (9—42)
            Range 0—42
    Total days supplied MOUD (method 2) 7472 (100.00)
            Median (interquartile range) 98 (56—125)
            Range 1—132
    Total days supplied MOUD before delivery (method 2) 7472 (100.00)
            Median (interquartile range) 74 (35—90)
            Range 0—90
    Total days supplied MOUD after delivery (method 2) 7472 (100.00)
            Median (interquartile range) 30 (14—42)
            Range 0—42
    Total days supplied MOUD (method 3) 7472 (100.00)
            Median (interquartile range) 89 (47—112)
            Range 1—132
    Total days supplied MOUD before delivery (method 3) 7472 (100.00)
            Median (interquartile range) 62 (30—78)
            Range 0—90
    Total days supplied MOUD after delivery (method 3) 7472 (100.00)
            Median (interquartile range) 30 (13—40)
            Range 0—42
    Avg dose pre-delivery (mg) 7394 (98.96)
            Median (interquartile range) 14.24 (8.00—16.00)
            Range 0.00—50.00
    Avg dose post-delivery (mg) 7394 (98.96)
            Median (interquartile range) 9.72 (4.00—16.00)
            Range 0.00—53.57
    Avg dose exposure (mg) 7394 (98.96)
            Median (interquartile range) 14.09 (9.42—16.00)
            Range 0.14—53.57
    Total days buprenorphine before delivery (method 3) 7299 (97.68)
            Median (interquartile range) 63.00 (30.00—78.00)
            Range 0.00—90.00
    Total days buprenorphine after delivery (method 3) 7299 (97.68)
            Median (interquartile range) 30.00 (13.00—41.00)
            Range 0.00—42.00
    Total days supplied buprenorphine 7299 (97.68)
            Median (interquartile range) 90.00 (49.00—112.00)
            Range 1.00—132.00
    Avg dose BUP pre-delivery (mg) 7298 (97.67)
            Median (interquartile range) 14.12 (8.00—16.00)
            Range 0.00—35.42
    Avg dose BUP post-delivery (mg) 7298 (97.67)
            Median (interquartile range) 9.71 (4.00—16.00)
            Range 0.00—42.67
    Avg dose BUP exposure (mg) 7298 (97.67)
            Median (interquartile range) 13.98 (9.13—16.00)
            Range 0.14—42.67
    Combined pain : Yes 7472 (100.00) 5766/7472 (77.17)
    Schizophrenia or personality disorder : Yes 7472 (100.00)     583/7472 (7.80)
    Alcohol or other substance use : Yes 7472 (100.00) 3342/7472 (44.73)
    Benzodiazepine or anticonvulsant use : Yes 7472 (100.00) 1077/7472 (14.41)
    Maternal morbidity : Yes 7472 (100.00)     528/7472 (7.07)
    Anxiety and depression combined : Yes 7472 (100.00) 3485/7472 (46.64)
    Back pain : Yes 7472 (100.00) 2528/7472 (33.83)
    Depression : Yes 7472 (100.00) 2946/7472 (39.43)
    Bipolar disorder : Yes 7472 (100.00)     819/7472 (10.96)
    Other substance use : Yes 7472 (100.00) 3197/7472 (42.79)
    Tobacco use : Yes 7472 (100.00) 5196/7472 (69.54)
    Med NSAIDS : Yes 7472 (100.00) 4602/7472 (61.59)
    Schizophrenia psychotic disorders : Yes 7472 (100.00)     466/7472 (6.24)
    Anxiety : Yes 7472 (100.00) 1608/7472 (21.52)
    Med benzodiazepine use : Yes 7472 (100.00)     713/7472 (9.54)
    Maternal morbidity : Yes 7472 (100.00)     528/7472 (7.07)
    Dental pain : Yes 7472 (100.00)     298/7472 (3.99)
    Alcohol use disorder : Yes 7472 (100.00)     507/7472 (6.79)
    Med anticonvulsant use : Yes 7472 (100.00)     432/7472 (5.78)
    Med muscle relaxant use : Yes 7472 (100.00)     371/7472 (4.97)
    Personality disorder : Yes 7472 (100.00)     220/7472 (2.94)
    Fibromyalgia : Yes 7472 (100.00)     383/7472 (5.13)
    CDC SVI overall percentile ranking of all 4 themes 7042 (94.25)
            Median (interquartile range) 0.58 (0.37—0.79)
            Range 0.00—1.00
    N is the number of non-missing value. 1Kruskal-Wallis. 2Pearson. 3Wilcoxon.

5.2 By cases

N No outcome Had outcome Test Statistic
(N=7345) (N=127)
Year of delivery 7472 (100.00) F1,7470=36.05, P<0.00013
        Median (interquartile range) 2016 (2014—2018) 2018 (2016—2019)
        Range 2007—2020 2007—2020
Age at delivery 7472 (100.00) F1,7470=0.04, P=0.83303
        Median (interquartile range) 27 (24—31) 27 (25—31)
        Range 17—44 19—41
Number of Gestation weeks 7472 (100.00) F1,7470=3.29, P=0.06983
        Median (interquartile range) 39 (37—39) 38 (37—39)
        Range 21—42 25—42
Race 7472 (100.00) Χ2
4
=31.51, P<0.00012
        American Indian or Alaska Native     22/7345 (0.30)     1/127 (0.79)
        Asian or Pacific Islander     11/7345 (0.15)     0/127 (0.00)
        Black of African American     205/7345 (2.79)     5/127 (3.94)
        Other or Unknown     47/7345 (0.64)     6/127 (4.72)
        White 7060/7345 (96.12) 115/127 (90.55)
Hispanic : Not Hispanic 7465 (99.91) 7273/7338 (99.11) 125/127 (98.43) Χ2
1
=0.67, P=0.41432
Race/Ethnicity combined 7472 (100.00) Χ2
4
=29.81, P<0.00012
        Hispanic     65/7345 (0.88)     2/127 (1.57)
        Non-Hispanic Asian     11/7345 (0.15)     0/127 (0.00)
        Non-Hispanic Black     204/7345 (2.78)     5/127 (3.94)
        Non-Hispanic Other     49/7345 (0.67)     6/127 (4.72)
        Non-Hispanic White 7016/7345 (95.52) 114/127 (89.76)
Route of delivery : Vaginal 7472 (100.00) 4774/7345 (65.00)     83/127 (65.35) Χ2
1
=0.01, P=0.93322
Number of previous pregnancies 7335 (98.17) F1,7333=0.97, P=0.32553
        Median (interquartile range) 2 (1—3) 2 (1—3)
        Range 0—23 0—11
Final outcome 7472 (100.00) Χ2
3
=7472.00, P<0.00012
        Death         0/7345 (0.00)     30/127 (23.62)
        Overdose         0/7345 (0.00)     97/127 (76.38)
        Loss of enrollment     709/7345 (9.65)     0/127 (0.00)
        Censored 6636/7345 (90.35)     0/127 (0.00)
Final outcome (w/o all payer data) 7472 (100.00) Χ2
3
=6026.67, P<0.00012
        Death         0/7345 (0.00)     11/127 (8.66)
        Overdose         0/7345 (0.00)     91/127 (71.65)
        Loss of enrollment     709/7345 (9.65)     25/127 (19.69)
        Censored 6636/7345 (90.35)     0/127 (0.00)
Total days supplied MOUD (method 3) 7472 (100.00) F1,7470=11.45, P=0.00073
        Median (interquartile range) 89 (47—112) 73 (30—104)
        Range 1—132 2—131
Total days supplied MOUD before delivery (method 3) 7472 (100.00) F1,7470=4.92, P=0.02653
        Median (interquartile range) 62 (30—78) 53 (17—77)
        Range 0—90 0—89
Total days supplied MOUD after delivery (method 3) 7472 (100.00) F1,7470=15.99, P=0.00013
        Median (interquartile range) 30 (13—41) 21 (5—35)
        Range 0—42 0—42
Avg dose pre-delivery (mg) 7394 (98.96) F1,7392=0.18, P=0.67513
        Median (interquartile range) 14.25 (8.00—16.00) 13.20 (8.00—16.00)
        Range 0.00—50.00 0.00—50.00
Avg dose post-delivery (mg) 7394 (98.96) F1,7392=0.98, P=0.32173
        Median (interquartile range) 9.76 (4.00—16.00) 8.94 (0.00—16.00)
        Range 0.00—53.57 0.00—24.00
Avg dose exposure (mg) 7394 (98.96) F1,7392=0.51, P=0.47583
        Median (interquartile range) 14.09 (9.43—16.00) 13.96 (8.74—16.00)
        Range 0.14—53.57 1.00—50.00
Total days buprenorphine before delivery (method 3) 7299 (97.68) F1,7297=7.19, P=0.00743
        Median (interquartile range) 63.00 (30.00—78.00) 49.00 (16.00—76.33)
        Range 0.00—90.00 0.00—89.00
Total days buprenorphine after delivery (method 3) 7299 (97.68) F1,7297=21.00, P<0.00013
        Median (interquartile range) 30.00 (13.00—41.00) 18.00 (3.33—34.33)
        Range 0.00—42.00 0.00—42.00
Total days supplied buprenorphine 7299 (97.68) F1,7297=15.41, P=0.00013
        Median (interquartile range) 90.00 (49.00—112.00) 71.00 (28.00—103.33)
        Range 1.00—132.00 2.00—131.00
Avg dose BUP pre-delivery (mg) 7298 (97.67) F1,7296=0.80, P=0.36993
        Median (interquartile range) 14.13 (8.00—16.00) 12.66 (8.00—16.00)
        Range 0.00—35.42 0.00—24.24
Avg dose BUP post-delivery (mg) 7298 (97.67) F1,7296=0.49, P=0.48323
        Median (interquartile range) 9.71 (4.00—16.00) 9.13 (0.00—16.00)
        Range 0.00—42.67 0.00—24.00
Avg dose BUP exposure (mg) 7298 (97.67) F1,7296=0.16, P=0.68873
        Median (interquartile range) 13.98 (9.14—16.00) 13.40 (8.67—16.00)
        Range 0.14—42.67 1.00—24.20
Combined pain : Yes 7472 (100.00) 5677/7345 (77.29)     89/127 (70.08) Χ2
1
=3.69, P=0.05492
Schizophrenia or personality disorder : Yes 7472 (100.00)     564/7345 (7.68)     19/127 (14.96) Χ2
1
=9.20, P=0.00242
Alcohol or other substance use : Yes 7472 (100.00) 3275/7345 (44.59)     67/127 (52.76) Χ2
1
=3.37, P=0.06642
Benzodiazepine or anticonvulsant use : Yes 7472 (100.00) 1052/7345 (14.32)     25/127 (19.69) Χ2
1
=2.91, P=0.08802
Maternal morbidity : Yes 7472 (100.00)     519/7345 (7.07)     9/127 (7.09) Χ2
1
=0.00, P=0.99282
Anxiety and depression combined : Yes 7472 (100.00) 3400/7345 (46.29)     85/127 (66.93) Χ2
1
=21.37, P<0.00012
Back pain : Yes 7472 (100.00) 2496/7345 (33.98)     32/127 (25.20) Χ2
1
=4.30, P=0.03802
Depression : Yes 7472 (100.00) 2868/7345 (39.05)     78/127 (61.42) Χ2
1
=26.16, P<0.00012
Bipolar disorder : Yes 7472 (100.00)     790/7345 (10.76)     29/127 (22.83) Χ2
1
=18.66, P<0.00012
Other substance use : Yes 7472 (100.00) 3130/7345 (42.61)     67/127 (52.76) Χ2
1
=5.25, P=0.02202
Tobacco use : Yes 7472 (100.00) 5101/7345 (69.45)     95/127 (74.80) Χ2
1
=1.69, P=0.19362
Med NSAIDS : Yes 7472 (100.00) 4530/7345 (61.67)     72/127 (56.69) Χ2
1
=1.31, P=0.25252
Schizophrenia psychotic disorders : Yes 7472 (100.00)     448/7345 (6.10)     18/127 (14.17) Χ2
1
=13.92, P=0.00022
Anxiety : Yes 7472 (100.00) 1562/7345 (21.27)     46/127 (36.22) Χ2
1
=16.53, P<0.00012
Med benzodiazepine use : Yes 7472 (100.00)     701/7345 (9.54)     12/127 (9.45) Χ2
1
=0.00, P=0.97122
Maternal morbidity : Yes 7472 (100.00)     519/7345 (7.07)     9/127 (7.09) Χ2
1
=0.00, P=0.99282
Dental pain : Yes 7472 (100.00)     291/7345 (3.96)     7/127 (5.51) Χ2
1
=0.78, P=0.37622
Alcohol use disorder : Yes 7472 (100.00)     485/7345 (6.60)     22/127 (17.32) Χ2
1
=22.68, P<0.00012
Med anticonvulsant use : Yes 7472 (100.00)     416/7345 (5.66)     16/127 (12.60) Χ2
1
=11.02, P=0.00092
Med muscle relaxant use : Yes 7472 (100.00)     363/7345 (4.94)     8/127 (6.30) Χ2
1
=0.49, P=0.48522
Personality disorder : Yes 7472 (100.00)     214/7345 (2.91)     6/127 (4.72) Χ2
1
=1.43, P=0.23132
Fibromyalgia : Yes 7472 (100.00)     376/7345 (5.12)     7/127 (5.51) Χ2
1
=0.04, P=0.84232
CDC SVI overall percentile ranking of all 4 themes 7042 (94.25) F1,7040=0.80, P=0.37143
        Median (interquartile range) 0.58 (0.37—0.79) 0.54 (0.31—0.83)
        Range 0.00—1.00 0.00—1.00
N is the number of non-missing value. 1Kruskal-Wallis. 2Pearson. 3Wilcoxon.


5.3 MOUD information

N All
(N=7472)
MOUD pre-delivery (method 1) 7472 (100.00)
        No MOUD     634/7472 (8.49)
        MOUD 6838/7472 (91.51)
MOUD pre-delivery (method 2) 7472 (100.00)
        No MOUD     634/7472 (8.49)
        MOUD 6838/7472 (91.51)
MOUD pre-delivery (method 3) 7472 (100.00)
        No MOUD     638/7472 (8.54)
        MOUD 6834/7472 (91.46)
MOUD post-delivery (method 1) 7472 (100.00)
        No MOUD 1494/7472 (19.99)
        MOUD 5978/7472 (80.01)
MOUD post-delivery (method 2) 7472 (100.00)
        No MOUD 1300/7472 (17.40)
        MOUD 6172/7472 (82.60)
MOUD post-delivery (method 3) 7472 (100.00)
        No MOUD     898/7472 (12.02)
        MOUD 6574/7472 (87.98)
MOUD pre and post (method 1) 7472 (100.00)
        No MOUD         0/7472 (0.00)
        Both pre and post 5344/7472 (71.52)
        Either pre or post 2128/7472 (28.48)
MOUD pre and post (method 2) 7472 (100.00)
        No MOUD         0/7472 (0.00)
        Both pre and post 5538/7472 (74.12)
        Either pre or post 1934/7472 (25.88)
MOUD pre and post (method 3) 7472 (100.00)
        No MOUD         0/7472 (0.00)
        Both pre and post 5936/7472 (79.44)
        Either pre or post 1536/7472 (20.56)
N is the number of non-missing value. 1Kruskal-Wallis. 2Pearson. 3Wilcoxon.


5.4 Characteristics based on MOUD timing (method 3)

5.4.1 Two categories

N Both pre and post Either pre or post Test Statistic
(N=5936) (N=1536)
Year of delivery 7472 (100.00) F1,7470=6.08, P=0.01373
        Median (interquartile range) 2016 (2014—2018) 2016 (2014—2018)
        Range 2007—2020 2007—2020
Year of delivery as categorical 7472 (100.00) Χ2
13
=53.65, P<0.00012
        2007     25/5936 (0.42)         7/1536 (0.46)
        2008     41/5936 (0.69)     18/1536 (1.17)
        2009     52/5936 (0.88)     29/1536 (1.89)
        2010     112/5936 (1.89)     30/1536 (1.95)
        2011     146/5936 (2.46)     46/1536 (2.99)
        2012     223/5936 (3.76)     47/1536 (3.06)
        2013     438/5936 (7.38)     83/1536 (5.40)
        2014     684/5936 (11.52)     127/1536 (8.27)
        2015     821/5936 (13.83)     181/1536 (11.78)
        2016     769/5936 (12.95)     216/1536 (14.06)
        2017     635/5936 (10.70)     194/1536 (12.63)
        2018     621/5936 (10.46)     183/1536 (11.91)
        2019     663/5936 (11.17)     204/1536 (13.28)
        2020     706/5936 (11.89)     171/1536 (11.13)
Age at delivery 7472 (100.00) F1,7470=0.46, P=0.49643
        Median (interquartile range) 27 (24—31) 27 (24—31)
        Range 17—44 17—44
Number of Gestation weeks 7472 (100.00) F1,7470=20.74, P<0.00013
        Median (interquartile range) 39 (37—39) 38 (37—39)
        Range 21—42 23—42
Race 7472 (100.00) Χ2
4
=10.38, P=0.03462
        American Indian or Alaska Native     16/5936 (0.27)         7/1536 (0.46)
        Asian or Pacific Islander         9/5936 (0.15)         2/1536 (0.13)
        Black of African American     153/5936 (2.58)     57/1536 (3.71)
        Other or Unknown     37/5936 (0.62)     16/1536 (1.04)
        White 5721/5936 (96.38) 1454/1536 (94.66)
Hispanic : Not Hispanic 7465 (99.91) 5879/5933 (99.09) 1519/1532 (99.15) Χ2
1
=0.05, P=0.81972
Race/Ethnicity combined 7472 (100.00) Χ2
4
=13.85, P=0.00782
        Hispanic     54/5936 (0.91)     13/1536 (0.85)
        Non-Hispanic Asian         9/5936 (0.15)         2/1536 (0.13)
        Non-Hispanic Black     153/5936 (2.58)     56/1536 (3.65)
        Non-Hispanic Other     35/5936 (0.59)     20/1536 (1.30)
        Non-Hispanic White 5685/5936 (95.77) 1445/1536 (94.08)
Route of delivery : Vaginal 7472 (100.00) 3822/5936 (64.39) 1035/1536 (67.38) Χ2
1
=4.81, P=0.02822
Number of previous pregnancies 7335 (98.17) F1,7333=4.07, P=0.04383
        Median (interquartile range) 2 (1—3) 2 (1—3)
        Range 0—23 0—23
Final outcome 7472 (100.00) Χ2
3
=34.63, P<0.00012
        Death     25/5936 (0.42)         5/1536 (0.33)
        Overdose     62/5936 (1.04)     35/1536 (2.28)
        Loss of enrollment     519/5936 (8.74)     190/1536 (12.37)
        Censored 5330/5936 (89.79) 1306/1536 (85.03)
Final outcome 3 levels 7472 (100.00) Χ2
2
=14.76, P=0.00062
        Death     25/5936 (0.42)         5/1536 (0.33)
        Overdose     62/5936 (1.04)     35/1536 (2.28)
        Censored 5849/5936 (98.53) 1496/1536 (97.40)
Total days supplied MOUD 7472 (100.00) F1,7470=5071.00, P<0.00013
        Median (interquartile range) 108 (84—122) 29 (14—42)
        Range 7—132 1—90
Total days supplied MOUD before delivery 7472 (100.00) F1,7470=3779.50, P<0.00013
        Median (interquartile range) 84 (60—90) 11 (0—35)
        Range 1—90 0—90
Total days supplied MOUD after delivery 7472 (100.00) F1,7470=1748.75, P<0.00013
        Median (interquartile range) 30 (21—42) 0 (0—21)
        Range 0—42 0—42
Total days supplied MOUD (method 2) 7472 (100.00) F1,7470=4954.77, P<0.00013
        Median (interquartile range) 112 (84—129) 29 (14—42)
        Range 7—132 1—132
Total days supplied MOUD before delivery (method 2) 7472 (100.00) F1,7470=3779.50, P<0.00013
        Median (interquartile range) 84 (60—90) 11 (0—35)
        Range 1—90 0—90
Total days supplied MOUD after delivery (method 2) 7472 (100.00) F1,7470=2132.86, P<0.00013
        Median (interquartile range) 35 (24—42) 0 (0—23)
        Range 0—42 0—42
Total days supplied MOUD (method 3) 7472 (100.00) F1,7470=5107.13, P<0.00013
        Median (interquartile range) 100 (76—116) 22 (11—34)
        Range 7—132 1—89
Total days supplied MOUD before delivery (method 3) 7472 (100.00) F1,7470=3154.36, P<0.00013
        Median (interquartile range) 69 (48—80) 10 (0—32)
        Range 1—90 0—89
Total days supplied MOUD after delivery (method 3) 7472 (100.00) F1,7470=4221.19, P<0.00013
        Median (interquartile range) 35 (23—41) 0 (0—11)
        Range 1—42 0—41
Avg dose pre-delivery (mg) 7394 (98.96) F1,7392=750.98, P<0.00013
        Median (interquartile range) 15.00 (9.94—16.00) 7.37 (0.00—16.00)
        Range 0.25—50.00 0.00—50.00
Avg dose post-delivery (mg) 7394 (98.96) F1,7392=858.54, P<0.00013
        Median (interquartile range) 12.00 (8.00—16.00) 0.00 (0.00—10.76)
        Range 0.00—50.00 0.00—53.57
Avg dose exposure (mg) 7394 (98.96) F1,7392=1.73, P=0.18813
        Median (interquartile range) 14.04 (9.87—16.00) 14.55 (8.00—16.00)
        Range 0.25—50.00 0.14—53.57
Total days buprenorphine before delivery (method 3) 7299 (97.68) F1,7297=2768.33, P<0.00013
        Median (interquartile range) 69.00 (48.00—80.00) 14.00 (0.00—33.00)
        Range 0.00—90.00 0.00—89.00
Total days buprenorphine after delivery (method 3) 7299 (97.68) F1,7297=3874.92, P<0.00013
        Median (interquartile range) 35.00 (23.00—41.00) 0.00 (0.00—9.00)
        Range 0.00—42.00 0.00—41.00
Total days supplied buprenorphine 7299 (97.68) F1,7297=4518.19, P<0.00013
        Median (interquartile range) 100.00 (76.00—116.00) 22.00 (11.17—35.00)
        Range 4.00—132.00 1.00—89.00
Avg dose BUP pre-delivery (mg) 7298 (97.67) F1,7296=753.31, P<0.00013
        Median (interquartile range) 14.86 (9.67—16.00) 7.47 (0.00—15.71)
        Range 0.00—35.42 0.00—29.71
Avg dose BUP post-delivery (mg) 7298 (97.67) F1,7296=927.21, P<0.00013
        Median (interquartile range) 12.00 (8.00—16.00) 0.00 (0.00—9.63)
        Range 0.00—33.24 0.00—42.67
Avg dose BUP exposure (mg) 7298 (97.67) F1,7296=0.00, P=0.99873
        Median (interquartile range) 13.98 (9.75—16.00) 14.00 (8.00—16.00)
        Range 0.25—34.47 0.14—42.67
Combined pain : Yes 7472 (100.00) 4591/5936 (77.34) 1175/1536 (76.50) Χ2
1
=0.49, P=0.48232
Schizophrenia or personality disorder : Yes 7472 (100.00)     434/5936 (7.31)     149/1536 (9.70) Χ2
1
=9.68, P=0.00192
Alcohol or other substance use : Yes 7472 (100.00) 2586/5936 (43.56)     756/1536 (49.22) Χ2
1
=15.78, P=0.00012
Benzodiazepine or anticonvulsant use : Yes 7472 (100.00)     859/5936 (14.47)     218/1536 (14.19) Χ2
1
=0.08, P=0.78192
Maternal morbidity : Yes 7472 (100.00)     407/5936 (6.86)     121/1536 (7.88) Χ2
1
=1.94, P=0.16392
Anxiety and depression combined : Yes 7472 (100.00) 2745/5936 (46.24)     740/1536 (48.18) Χ2
1
=1.83, P=0.17572
Back pain : Yes 7472 (100.00) 2030/5936 (34.20)     498/1536 (32.42) Χ2
1
=1.72, P=0.18972
Depression : Yes 7472 (100.00) 2314/5936 (38.98)     632/1536 (41.15) Χ2
1
=2.39, P=0.12202
Bipolar disorder : Yes 7472 (100.00)     648/5936 (10.92)     171/1536 (11.13) Χ2
1
=0.06, P=0.80882
Other substance use : Yes 7472 (100.00) 2460/5936 (41.44)     737/1536 (47.98) Χ2
1
=21.32, P<0.00012
Tobacco use : Yes 7472 (100.00) 4117/5936 (69.36) 1079/1536 (70.25) Χ2
1
=0.46, P=0.49892
Med NSAIDS : Yes 7472 (100.00) 3667/5936 (61.78)     935/1536 (60.87) Χ2
1
=0.42, P=0.51652
Schizophrenia psychotic disorders : Yes 7472 (100.00)     353/5936 (5.95)     113/1536 (7.36) Χ2
1
=4.15, P=0.04172
Anxiety : Yes 7472 (100.00) 1260/5936 (21.23)     348/1536 (22.66) Χ2
1
=1.48, P=0.22422
Med benzodiazepine use : Yes 7472 (100.00)     564/5936 (9.50)     149/1536 (9.70) Χ2
1
=0.06, P=0.81282
Maternal morbidity : Yes 7472 (100.00)     407/5936 (6.86)     121/1536 (7.88) Χ2
1
=1.94, P=0.16392
Dental pain : Yes 7472 (100.00)     224/5936 (3.77)     74/1536 (4.82) Χ2
1
=3.47, P=0.06232
Alcohol use disorder : Yes 7472 (100.00)     377/5936 (6.35)     130/1536 (8.46) Χ2
1
=8.61, P=0.00332
Med anticonvulsant use : Yes 7472 (100.00)     351/5936 (5.91)     81/1536 (5.27) Χ2
1
=0.92, P=0.33842
Med muscle relaxant use : Yes 7472 (100.00)     264/5936 (4.45)     107/1536 (6.97) Χ2
1
=16.41, P=0.00012
Personality disorder : Yes 7472 (100.00)     154/5936 (2.59)     66/1536 (4.30) Χ2
1
=12.38, P=0.00042
Fibromyalgia : Yes 7472 (100.00)     299/5936 (5.04)     84/1536 (5.47) Χ2
1
=0.47, P=0.49412
CDC SVI overall percentile ranking of all 4 themes 7042 (94.25) F1,7040=3.35, P=0.06733
        Median (interquartile range) 0.57 (0.36—0.78) 0.60 (0.38—0.80)
        Range 0.00—1.00 0.00—1.00
N is the number of non-missing value. 1Kruskal-Wallis. 2Pearson. 3Wilcoxon.


5.4.2 Three categories

N Only pre Only post Both pre and post Test Statistic
(N=898) (N=638) (N=5936)
Year of delivery 7472 (100.00) F2,7469=4.01, P=0.01821
        Median (interquartile range) 2016 (2015—2018) 2016 (2014—2019) 2016 (2014—2018)
        Range 2007—2020 2007—2020 2007—2020
Year of delivery as categorical 7472 (100.00) Χ2
26
=167.95, P<0.00012
        2007     1/898 (0.11)     6/638 (0.94)     25/5936 (0.42)
        2008     3/898 (0.33)     15/638 (2.35)     41/5936 (0.69)
        2009     10/898 (1.11)     19/638 (2.98)     52/5936 (0.88)
        2010     6/898 (0.67)     24/638 (3.76)     112/5936 (1.89)
        2011     19/898 (2.12)     27/638 (4.23)     146/5936 (2.46)
        2012     28/898 (3.12)     19/638 (2.98)     223/5936 (3.76)
        2013     40/898 (4.45)     43/638 (6.74)     438/5936 (7.38)
        2014     79/898 (8.80)     48/638 (7.52)     684/5936 (11.52)
        2015 121/898 (13.47)     60/638 (9.40)     821/5936 (13.83)
        2016 155/898 (17.26)     61/638 (9.56)     769/5936 (12.95)
        2017 124/898 (13.81)     70/638 (10.97)     635/5936 (10.70)
        2018 125/898 (13.92)     58/638 (9.09)     621/5936 (10.46)
        2019 113/898 (12.58)     91/638 (14.26)     663/5936 (11.17)
        2020     74/898 (8.24)     97/638 (15.20)     706/5936 (11.89)
Age at delivery 7472 (100.00) F2,7469=0.32, P=0.72301
        Median (interquartile range) 27 (24—31) 27 (24—31) 27 (24—31)
        Range 18—43 17—44 17—44
Number of Gestation weeks 7472 (100.00) F2,7469=13.25, P<0.00011
        Median (interquartile range) 39 (37—39) 38 (37—39) 39 (37—39)
        Range 24—42 23—42 21—42
Race 7472 (100.00) Χ2
8
=11.75, P=0.16262
        American Indian or Alaska Native     4/898 (0.45)     3/638 (0.47)     16/5936 (0.27)
        Asian or Pacific Islander     1/898 (0.11)     1/638 (0.16)         9/5936 (0.15)
        Black of African American     35/898 (3.90)     22/638 (3.45)     153/5936 (2.58)
        Other or Unknown     11/898 (1.22)     5/638 (0.78)     37/5936 (0.62)
        White 847/898 (94.32) 607/638 (95.14) 5721/5936 (96.38)
Hispanic : Not Hispanic 7465 (99.91) 886/895 (98.99) 633/637 (99.37) 5879/5933 (99.09) Χ2
2
=0.65, P=0.72302
Race/Ethnicity combined 7472 (100.00) Χ2
8
=15.31, P=0.05342
        Hispanic     9/898 (1.00)     4/638 (0.63)     54/5936 (0.91)
        Non-Hispanic Asian     1/898 (0.11)     1/638 (0.16)         9/5936 (0.15)
        Non-Hispanic Black     34/898 (3.79)     22/638 (3.45)     153/5936 (2.58)
        Non-Hispanic Other     13/898 (1.45)     7/638 (1.10)     35/5936 (0.59)
        Non-Hispanic White 841/898 (93.65) 604/638 (94.67) 5685/5936 (95.77)
Route of delivery : Vaginal 7472 (100.00) 614/898 (68.37) 421/638 (65.99) 3822/5936 (64.39) Χ2
2
=5.75, P=0.05652
Number of previous pregnancies 7335 (98.17) F2,7332=2.23, P=0.10741
        Median (interquartile range) 2 (1—3) 2 (1—3) 2 (1—3)
        Range 0—19 0—23 0—23
Final outcome 7472 (100.00) Χ2
6
=39.01, P<0.00012
        Death     3/898 (0.33)     2/638 (0.31)     25/5936 (0.42)
        Overdose     19/898 (2.12)     16/638 (2.51)     62/5936 (1.04)
        Loss of enrollment 100/898 (11.14)     90/638 (14.11)     519/5936 (8.74)
        Censored 776/898 (86.41) 530/638 (83.07) 5330/5936 (89.79)
Final outcome 3 levels 7472 (100.00) Χ2
4
=15.21, P=0.00432
        Death     3/898 (0.33)     2/638 (0.31)     25/5936 (0.42)
        Overdose     19/898 (2.12)     16/638 (2.51)     62/5936 (1.04)
        Censored 876/898 (97.55) 620/638 (97.18) 5849/5936 (98.53)
Total days supplied MOUD 7472 (100.00) F2,7469=2556.49, P<0.00011
        Median (interquartile range) 30 (15—56) 28 (14—33) 108 (84—122)
        Range 1—90 1—70 7—132
Total days supplied MOUD before delivery 7472 (100.00) F2,7469=2174.12, P<0.00011
        Median (interquartile range) 30 (15—56) 0 (0—0) 84 (60—90)
        Range 1—90 0—28 1—90
Total days supplied MOUD after delivery 7472 (100.00) F2,7469=1437.41, P<0.00011
        Median (interquartile range) 0 (0—0) 28 (14—33) 30 (21—42)
        Range 0—0 1—42 0—42
Total days supplied MOUD (method 2) 7472 (100.00) F2,7469=2502.29, P<0.00011
        Median (interquartile range) 30 (15—56) 28 (14—33) 112 (84—129)
        Range 1—132 1—70 7—132
Total days supplied MOUD before delivery (method 2) 7472 (100.00) F2,7469=2174.12, P<0.00011
        Median (interquartile range) 30 (15—56) 0 (0—0) 84 (60—90)
        Range 1—90 0—28 1—90
Total days supplied MOUD after delivery (method 2) 7472 (100.00) F2,7469=1572.78, P<0.00011
        Median (interquartile range) 0 (0—0) 28 (14—33) 35 (24—42)
        Range 0—42 1—42 0—42
Total days supplied MOUD (method 3) 7472 (100.00) F2,7469=2608.87, P<0.00011
        Median (interquartile range) 30 (14—49) 14 (7—25) 100 (76—116)
        Range 1—89 1—41 7—132
Total days supplied MOUD before delivery (method 3) 7472 (100.00) F2,7469=1884.96, P<0.00011
        Median (interquartile range) 30 (14—49) 0 (0—0) 69 (48—80)
        Range 1—89 0—0 1—90
Total days supplied MOUD after delivery (method 3) 7472 (100.00) F2,7469=2453.64, P<0.00011
        Median (interquartile range) 0 (0—0) 14 (7—25) 35 (23—41)
        Range 0—0 1—41 1—42
Avg dose pre-delivery (mg) 7394 (98.96) F2,7391=1043.59, P<0.00011
        Median (interquartile range) 13.90 (8.00—16.00) 0.00 (0.00—0.00) 15.00 (9.94—16.00)
        Range 0.14—50.00 0.00—0.00 0.25—50.00
Avg dose post-delivery (mg) 7394 (98.96) F2,7391=1408.35, P<0.00011
        Median (interquartile range) 0.00 (0.00—0.00) 15.76 (8.12—16.00) 12.00 (8.00—16.00)
        Range 0.00—0.00 0.80—53.57 0.00—50.00
Avg dose exposure (mg) 7394 (98.96) F2,7391=6.55, P=0.00141
        Median (interquartile range) 13.90 (8.00—16.00) 15.76 (8.12—16.00) 14.04 (9.87—16.00)
        Range 0.14—50.00 0.80—53.57 0.25—50.00
Total days buprenorphine before delivery (method 3) 7299 (97.68) F2,7296=1632.75, P<0.00011
        Median (interquartile range) 30.00 (14.00—49.00) 0.00 (0.00—0.00) 69.00 (48.00—80.00)
        Range 1.00—89.00 0.00—0.00 0.00—90.00
Total days buprenorphine after delivery (method 3) 7299 (97.68) F2,7296=2232.06, P<0.00011
        Median (interquartile range) 0.00 (0.00—0.00) 14.50 (7.00—25.00) 35.00 (23.00—41.00)
        Range 0.00—0.00 1.00—41.00 0.00—42.00
Total days supplied buprenorphine 7299 (97.68) F2,7296=2300.69, P<0.00011
        Median (interquartile range) 30.00 (14.00—49.00) 14.50 (7.00—25.00) 100.00 (76.00—116.00)
        Range 1.00—89.00 1.00—41.00 4.00—132.00
Avg dose BUP pre-delivery (mg) 7298 (97.67) F2,7295=997.58, P<0.00011
        Median (interquartile range) 13.33 (8.00—16.00) 0.00 (0.00—0.00) 14.86 (9.67—16.00)
        Range 0.14—29.71 0.00—0.00 0.00—35.42
Avg dose BUP post-delivery (mg) 7298 (97.67) F2,7295=1365.44, P<0.00011
        Median (interquartile range) 0.00 (0.00—0.00) 15.30 (8.00—16.00) 12.00 (8.00—16.00)
        Range 0.00—0.00 0.80—42.67 0.00—33.24
Avg dose BUP exposure (mg) 7298 (97.67) F2,7295=3.99, P=0.01851
        Median (interquartile range) 13.33 (8.00—16.00) 15.30 (8.00—16.00) 13.98 (9.75—16.00)
        Range 0.14—29.71 0.80—42.67 0.25—34.47
Combined pain : Yes 7472 (100.00) 702/898 (78.17) 473/638 (74.14) 4591/5936 (77.34) Χ2
2
=3.94, P=0.13932
Schizophrenia or personality disorder : Yes 7472 (100.00)     83/898 (9.24)     66/638 (10.34)     434/5936 (7.31) Χ2
2
=10.31, P=0.00582
Alcohol or other substance use : Yes 7472 (100.00) 441/898 (49.11) 315/638 (49.37) 2586/5936 (43.56) Χ2
2
=15.79, P=0.00042
Benzodiazepine or anticonvulsant use : Yes 7472 (100.00) 131/898 (14.59)     87/638 (13.64)     859/5936 (14.47) Χ2
2
=0.35, P=0.83932
Maternal morbidity : Yes 7472 (100.00)     69/898 (7.68)     52/638 (8.15)     407/5936 (6.86) Χ2
2
=2.06, P=0.35682
Anxiety and depression combined : Yes 7472 (100.00) 403/898 (44.88) 337/638 (52.82) 2745/5936 (46.24) Χ2
2
=11.29, P=0.00352
Back pain : Yes 7472 (100.00) 308/898 (34.30) 190/638 (29.78) 2030/5936 (34.20) Χ2
2
=5.12, P=0.07732
Depression : Yes 7472 (100.00) 338/898 (37.64) 294/638 (46.08) 2314/5936 (38.98) Χ2
2
=13.52, P=0.00122
Bipolar disorder : Yes 7472 (100.00) 110/898 (12.25)     61/638 (9.56)     648/5936 (10.92) Χ2
2
=2.82, P=0.24412
Other substance use : Yes 7472 (100.00) 434/898 (48.33) 303/638 (47.49) 2460/5936 (41.44) Χ2
2
=21.43, P<0.00012
Tobacco use : Yes 7472 (100.00) 651/898 (72.49) 428/638 (67.08) 4117/5936 (69.36) Χ2
2
=5.61, P=0.06052
Med NSAIDS : Yes 7472 (100.00) 551/898 (61.36) 384/638 (60.19) 3667/5936 (61.78) Χ2
2
=0.64, P=0.72732
Schizophrenia psychotic disorders : Yes 7472 (100.00)     64/898 (7.13)     49/638 (7.68)     353/5936 (5.95) Χ2
2
=4.34, P=0.11402
Anxiety : Yes 7472 (100.00) 208/898 (23.16) 140/638 (21.94) 1260/5936 (21.23) Χ2
2
=1.81, P=0.40552
Med benzodiazepine use : Yes 7472 (100.00)     93/898 (10.36)     56/638 (8.78)     564/5936 (9.50) Χ2
2
=1.13, P=0.56742
Maternal morbidity : Yes 7472 (100.00)     69/898 (7.68)     52/638 (8.15)     407/5936 (6.86) Χ2
2
=2.06, P=0.35682
Dental pain : Yes 7472 (100.00)     44/898 (4.90)     30/638 (4.70)     224/5936 (3.77) Χ2
2
=3.51, P=0.17272
Alcohol use disorder : Yes 7472 (100.00)     66/898 (7.35)     64/638 (10.03)     377/5936 (6.35) Χ2
2
=12.85, P=0.00162
Med anticonvulsant use : Yes 7472 (100.00)     48/898 (5.35)     33/638 (5.17)     351/5936 (5.91) Χ2
2
=0.94, P=0.62602
Med muscle relaxant use : Yes 7472 (100.00)     57/898 (6.35)     50/638 (7.84)     264/5936 (4.45) Χ2
2
=18.16, P=0.00012
Personality disorder : Yes 7472 (100.00)     35/898 (3.90)     31/638 (4.86)     154/5936 (2.59) Χ2
2
=13.58, P=0.00112
Fibromyalgia : Yes 7472 (100.00)     55/898 (6.12)     29/638 (4.55)     299/5936 (5.04) Χ2
2
=2.38, P=0.30412
CDC SVI overall percentile ranking of all 4 themes 7042 (94.25) F2,7039=2.85, P=0.05801
        Median (interquartile range) 0.61 (0.38—0.81) 0.58 (0.37—0.78) 0.57 (0.36—0.78)
        Range 0.00—1.00 0.00—1.00 0.00—1.00
N is the number of non-missing value. 1Kruskal-Wallis. 2Pearson. 3Wilcoxon.


5.5 Histogram of MOUD days supplied

5.5.1 Before delivery up to 90 days (Method 1)

5.5.2 Before delivery up to 90 days (Method 2)


5.5.3 Before delivery up to 90 days (Method 3)


5.5.4 After delivery up to 41 days (Method 1)

5.5.5 After delivery up to 41 days (Method 3)


5.5.6 After delivery up to 41 days (Method 3)


5.5.7 Entire exposure (Method 1)


5.5.8 Entire exposure (Method 2)


5.5.9 Entire exposure (Method 3)



Survival Analysis

5.6 Kaplan Meier Plot

Call: survfit(formula = Surv(days.to.event, outcome.bin) ~ 1, data = moud)

        n events median 0.95LCL 0.95UCL
[1,] 7472    127     NA      NA      NA

   Min. 1st Qu.  Median    Mean 3rd Qu.    Max. 
    2.0    97.0   185.0   178.3   261.0   323.0 
time probability
2 0.9998662
7 0.9997323
8 0.9994647
17 0.9993308
18 0.9991970
19 0.9990632
27 0.9989293
32 0.9987955
34 0.9986617
35 0.9983940
41 0.9982602
45 0.9979925
47 0.9978587
52 0.9977248
59 0.9974572
60 0.9973233
61 0.9971895
63 0.9970557
65 0.9969218
66 0.9967880
69 0.9966542
70 0.9965203
75 0.9963865
77 0.9962527
87 0.9961188
93 0.9959850
95 0.9958512
97 0.9957173
101 0.9954497
110 0.9953158
111 0.9951820
112 0.9950482
118 0.9949143
120 0.9947805
121 0.9946467
125 0.9945128
128 0.9943790
131 0.9942452
138 0.9939775
140 0.9938437
144 0.9937099
147 0.9935760
151 0.9933084
153 0.9931745
156 0.9929069
166 0.9927730
171 0.9926392
173 0.9925054
175 0.9923715
177 0.9922377
178 0.9921039
181 0.9919700
182 0.9918362
184 0.9917024
185 0.9915685
188 0.9913009
193 0.9911670
204 0.9910332
208 0.9908994
211 0.9907655
213 0.9906317
215 0.9904979
216 0.9903640
217 0.9900964
220 0.9899625
222 0.9898287
223 0.9896949
228 0.9894272
229 0.9892934
233 0.9891595
235 0.9890257
236 0.9888919
239 0.9887580
240 0.9884904
245 0.9883565
246 0.9880889
247 0.9879550
250 0.9878212
253 0.9876874
254 0.9875535
258 0.9874197
261 0.9871520
262 0.9870182
263 0.9868844
265 0.9867505
267 0.9866167
268 0.9864829
270 0.9863490
271 0.9862152
274 0.9859475
275 0.9858137
279 0.9856799
287 0.9854122
289 0.9852784
290 0.9851445
295 0.9850107
296 0.9848769
298 0.9846092
300 0.9844754
301 0.9843415
302 0.9842077
304 0.9840739
305 0.9839400
308 0.9836724
310 0.9834047
313 0.9832709
316 0.9831370
319 0.9830032
323 0.9830032


5.7 Time to event for overdose and death

Descriptives deathod$days.to.event
image
nmissingdistinctInfoMeanpMedianGmd.05.10.25.50.75.90.95
12701081178.4179108.1 21.4 43.4 99.0188.0261.0298.0307.1
lowest : 2 7 8 17 18 , highest: 308 310 313 316 319 Descriptives death$days.to.event
image
nmissingdistinctInfoMeanpMedianGmd.05.10.25.50.75.90.95
300301153.9154112.5 17.9 30.7 59.5163.5239.0275.4285.0
lowest : 2 17 19 32 35 , highest: 267 275 279 290 308 Descriptives od$days.to.event
image
nmissingdistinctInfoMeanpMedianGmd.05.10.25.50.75.90.95
970881186186.5106.1 32.6 54.2111.0208.0263.0300.4308.4
lowest : 7 8 18 27 34 , highest: 308 310 313 316 319

6 Multivariable Cox PH model

6.1 Linear continuous terms

Effects   Response: Surv(days.to.event, outcome.bin)
Low High Δ Effect S.E. Lower 0.95 Upper 0.95
Year of delivery 2016 2018 2 0.406700 0.09689 0.21680 0.59660
Hazard Ratio 2016 2018 2 1.502000 1.24200 1.81600
Total days supplied MOUD (method 3) 1 31 30 -0.192300 0.06460 -0.31890 -0.06565
Hazard Ratio 1 31 30 0.825100 0.72700 0.93650
Age at delivery 27 31 4 -0.092200 0.07947 -0.24800 0.06357
Hazard Ratio 27 31 4 0.911900 0.78040 1.06600
Number of Gestation weeks 39 37 -2 0.071680 0.07413 -0.07361 0.21700
Hazard Ratio 39 37 -2 1.074000 0.92900 1.24200
Route of delivery --- Cesarean:Vaginal 2 1 -0.005726 0.19320 -0.38440 0.37300
Hazard Ratio 2 1 0.994300 0.68080 1.45200
Combined pain --- Yes:No 1 2 -0.235200 0.19800 -0.62320 0.15290
Hazard Ratio 1 2 0.790400 0.53620 1.16500
Alcohol or other substance use --- Yes:No 1 2 0.324700 0.18550 -0.03882 0.68820
Hazard Ratio 1 2 1.384000 0.96190 1.99000
Benzodiazepine or anticonvulsant use --- Yes:No 1 2 0.355400 0.22380 -0.08325 0.79410
Hazard Ratio 1 2 1.427000 0.92010 2.21200
Anxiety and depression combined --- Yes:No 1 2 0.635600 0.20080 0.24200 1.02900
Hazard Ratio 1 2 1.888000 1.27400 2.79900
Maternal morbidity --- Yes:No 1 2 -0.001079 0.37710 -0.74020 0.73810
Hazard Ratio 1 2 0.998900 0.47700 2.09200
Wald Statistics for Surv(days.to.event, outcome.bin)
χ2 d.f. P
Year of delivery 17.59 1 <0.0001
Total days supplied MOUD (method 3) 8.85 1 0.0029
Age at delivery 1.35 1 0.2456
Route of delivery 0.00 1 0.9764
Number of Gestation weeks 0.94 1 0.3331
Combined pain 1.41 1 0.2350
Alcohol or other substance use 3.07 1 0.0800
Benzodiazepine or anticonvulsant use 2.52 1 0.1122
Anxiety and depression combined 10.01 1 0.0016
Maternal morbidity 0.00 1 0.9977
TOTAL 61.67 10 <0.0001


6.1.1 Univariable HR

Effects   Response: Surv(days.to.event, outcome.bin)
Low High Δ Effect S.E. Lower 0.95 Upper 0.95
Total days supplied MOUD (method 3) 1 31 30 -0.2263 0.06572 -0.3551 -0.09746
Hazard Ratio 1 31 30 0.7975 0.7011 0.90710
Wald Statistics for Surv(days.to.event, outcome.bin)
χ2 d.f. P
Total days supplied MOUD (method 3) 11.85 1 0.0006
TOTAL 11.85 1 0.0006

6.2 With splines

Effects   Response: Surv(days.to.event, outcome.bin)
Low High Δ Effect S.E. Lower 0.95 Upper 0.95
Year of delivery 2016 2018 2 0.467700 0.09835 0.27490 0.66050
Hazard Ratio 2016 2018 2 1.596000 1.31600 1.93600
Total days supplied MOUD (method 3) 1 31 30 -0.194100 0.06405 -0.31960 -0.06857
Hazard Ratio 1 31 30 0.823600 0.72640 0.93370
Age at delivery 27 31 4 -0.094170 0.07917 -0.24930 0.06100
Hazard Ratio 27 31 4 0.910100 0.77930 1.06300
Number of Gestation weeks 39 37 -2 0.069940 0.07470 -0.07647 0.21640
Hazard Ratio 39 37 -2 1.072000 0.92640 1.24200
Route of delivery --- Cesarean:Vaginal 2 1 -0.005208 0.19310 -0.38360 0.37320
Hazard Ratio 2 1 0.994800 0.68140 1.45200
Combined pain --- Yes:No 1 2 -0.246600 0.19930 -0.63730 0.14410
Hazard Ratio 1 2 0.781400 0.52870 1.15500
Alcohol or other substance use --- Yes:No 1 2 0.325300 0.18570 -0.03873 0.68940
Hazard Ratio 1 2 1.384000 0.96200 1.99200
Benzodiazepine or anticonvulsant use --- Yes:No 1 2 0.373200 0.22820 -0.07416 0.82050
Hazard Ratio 1 2 1.452000 0.92850 2.27200
Anxiety and depression combined --- Yes:No 1 2 0.640100 0.20040 0.24730 1.03300
Hazard Ratio 1 2 1.897000 1.28100 2.80900
Maternal morbidity --- Yes:No 1 2 -0.020030 0.37720 -0.75930 0.71930
Hazard Ratio 1 2 0.980200 0.46800 2.05300
Wald Statistics for Surv(days.to.event, outcome.bin)
χ2 d.f. P
Year of delivery 25.25 2 <0.0001
Nonlinear 1.17 1 0.2797
Total days supplied MOUD (method 3) 9.18 1 0.0024
Age at delivery 1.42 1 0.2338
Route of delivery 0.00 1 0.9785
Number of Gestation weeks 0.88 1 0.3486
Combined pain 1.53 1 0.2161
Alcohol or other substance use 3.07 1 0.0798
Benzodiazepine or anticonvulsant use 2.68 1 0.1019
Anxiety and depression combined 10.19 1 0.0014
Maternal morbidity 0.00 1 0.9576
TOTAL 71.22 11 <0.0001


6.3 Linear model (only buprenorphine)

Effects   Response: Surv(days.to.event, outcome.bin)
Low High Δ Effect S.E. Lower 0.95 Upper 0.95
Year of delivery 2016 2018 2 0.41000 0.09798 0.21800 0.60200
Hazard Ratio 2016 2018 2 1.50700 1.24400 1.82600
Total days supplied buprenorphine 1 31 30 -0.24020 0.06656 -0.37070 -0.10970
Hazard Ratio 1 31 30 0.78650 0.69030 0.89610
Age at delivery 27 31 4 -0.08383 0.07952 -0.23970 0.07202
Hazard Ratio 27 31 4 0.91960 0.78690 1.07500
Number of Gestation weeks 39 37 -2 0.07175 0.07370 -0.07269 0.21620
Hazard Ratio 39 37 -2 1.07400 0.92990 1.24100
Route of delivery --- Cesarean:Vaginal 2 1 -0.05152 0.19580 -0.43520 0.33220
Hazard Ratio 2 1 0.94980 0.64710 1.39400
Combined pain --- Yes:No 1 2 -0.24090 0.19880 -0.63040 0.14870
Hazard Ratio 1 2 0.78590 0.53240 1.16000
Alcohol or other substance use --- Yes:No 1 2 0.38810 0.18630 0.02293 0.75330
Hazard Ratio 1 2 1.47400 1.02300 2.12400
Benzodiazepine or anticonvulsant use --- Yes:No 1 2 0.36220 0.22470 -0.07817 0.80260
Hazard Ratio 1 2 1.43700 0.92480 2.23100
Anxiety and depression combined --- Yes:No 1 2 0.65110 0.20130 0.25650 1.04600
Hazard Ratio 1 2 1.91800 1.29200 2.84500
Maternal morbidity --- Yes:No 1 2 -0.01000 0.37850 -0.75180 0.73170
Hazard Ratio 1 2 0.99000 0.47150 2.07900
Wald Statistics for Surv(days.to.event, outcome.bin)
χ2 d.f. P
Year of delivery 17.48 1 <0.0001
Total days supplied buprenorphine 13.01 1 0.0003
Age at delivery 1.11 1 0.2914
Route of delivery 0.07 1 0.7925
Number of Gestation weeks 0.95 1 0.3297
Combined pain 1.47 1 0.2257
Alcohol or other substance use 4.34 1 0.0372
Benzodiazepine or anticonvulsant use 2.60 1 0.1068
Anxiety and depression combined 10.44 1 0.0012
Maternal morbidity 0.00 1 0.9789
TOTAL 66.41 10 <0.0001


6.3.1 Univariate

Effects   Response: Surv(days.to.event, outcome.bin)
Low High Δ Effect S.E. Lower 0.95 Upper 0.95
Total days supplied buprenorphine 1 31 30 -0.2751 0.06795 -0.4082 -0.1419
Hazard Ratio 1 31 30 0.7595 0.6648 0.8677
Wald Statistics for Surv(days.to.event, outcome.bin)
χ2 d.f. P
Total days supplied buprenorphine 16.37 1 <0.0001
TOTAL 16.37 1 <0.0001

By MOUD timing

7 Survival analysis

7.1 KM Curves

time probability
2 0.9988864
8 0.9977728
19 0.9966592
32 0.9955457
45 0.9944321
70 0.9933185
97 0.9922049
101 0.9910913
111 0.9899777
125 0.9888641
131 0.9877506
173 0.9866370
177 0.9855234
217 0.9844098
222 0.9832962
240 0.9821826
258 0.9810690
261 0.9799555
270 0.9788419
274 0.9777283
287 0.9766147
310 0.9755011
323 0.9755011
27 0.9984326
35 0.9968652
77 0.9952978
87 0.9937304
101 0.9921630
118 0.9905956
138 0.9890282
147 0.9874608
166 0.9858934
193 0.9843260
213 0.9827586
215 0.9811912
217 0.9796238
245 0.9780564
295 0.9764890
300 0.9749216
301 0.9733542
319 0.9717868
323 0.9717868
7 0.9998315
8 0.9996631
17 0.9994946
18 0.9993261
34 0.9991577
35 0.9989892
41 0.9988208
45 0.9986523
47 0.9984838
52 0.9983154
59 0.9979784
60 0.9978100
61 0.9976415
63 0.9974730
65 0.9973046
66 0.9971361
69 0.9969677
75 0.9967992
93 0.9966307
95 0.9964623
110 0.9962938
112 0.9961253
120 0.9959569
121 0.9957884
128 0.9956199
138 0.9954515
140 0.9952830
144 0.9951146
151 0.9947776
153 0.9946092
156 0.9942722
171 0.9941038
175 0.9939353
178 0.9937668
181 0.9935984
182 0.9934299
184 0.9932615
185 0.9930930
188 0.9927561
204 0.9925876
208 0.9924191
211 0.9922507
216 0.9920822
220 0.9919137
223 0.9917453
228 0.9914084
229 0.9912399
233 0.9910714
235 0.9909030
236 0.9907345
239 0.9905660
240 0.9903976
246 0.9900606
247 0.9898922
250 0.9897237
253 0.9895553
254 0.9893868
261 0.9892183
262 0.9890499
263 0.9888814
265 0.9887129
267 0.9885445
268 0.9883760
271 0.9882075
274 0.9880391
275 0.9878706
279 0.9877022
287 0.9875337
289 0.9873652
290 0.9871968
296 0.9870283
298 0.9866914
302 0.9865229
304 0.9863544
305 0.9861860
308 0.9858491
310 0.9856806
313 0.9855121
316 0.9853437
323 0.9853437

7.2 Log-Rank Test

Call:
survdiff(formula = Surv(days.to.event, outcome.bin) ~ moud.both3div, 
    data = moud)

                                   N Observed Expected (O-E)^2/E (O-E)^2/V
moud.both3div=Only pre           898       22     15.2      3.06      3.48
moud.both3div=Only post          638       18     10.8      4.83      5.28
moud.both3div=Both pre and post 5936       87    101.0      1.95      9.54

 Chisq= 9.8  on 2 degrees of freedom, p= 0.007 


7.3 Multivariable Cox PH model

Linear continuous terms (timing + days)

Effects   Response: Surv(days.to.event, outcome.bin)
Low High Δ Effect S.E. Lower 0.95 Upper 0.95
Total days supplied MOUD (method 3) 1 31 30 -0.142500 0.09738 -0.33340 0.04834
Hazard Ratio 1 31 30 0.867200 0.71650 1.05000
Year of delivery 2016 2018 2 0.405800 0.09657 0.21660 0.59510
Hazard Ratio 2016 2018 2 1.501000 1.24200 1.81300
Age at delivery 27 31 4 -0.095060 0.07930 -0.25050 0.06038
Hazard Ratio 27 31 4 0.909300 0.77840 1.06200
Number of Gestation weeks 39 37 -2 0.069880 0.07310 -0.07339 0.21310
Hazard Ratio 39 37 -2 1.072000 0.92920 1.23800
MOUD receipt timing --- Only pre:Both pre and post 3 1 0.198600 0.31710 -0.42290 0.82000
Hazard Ratio 3 1 1.220000 0.65510 2.27100
MOUD receipt timing --- Only post:Both pre and post 3 2 0.205500 0.34720 -0.47500 0.88610
Hazard Ratio 3 2 1.228000 0.62190 2.42600
Route of delivery --- Cesarean:Vaginal 2 1 -0.008465 0.19370 -0.38800 0.37110
Hazard Ratio 2 1 0.991600 0.67840 1.44900
Combined pain --- No:Yes 2 1 0.233900 0.19810 -0.15450 0.62220
Hazard Ratio 2 1 1.263000 0.85690 1.86300
Alcohol or other substance use --- Yes:No 1 2 0.328700 0.18510 -0.03412 0.69160
Hazard Ratio 1 2 1.389000 0.96650 1.99700
Benzodiazepine or anticonvulsant use --- Yes:No 1 2 0.355500 0.22380 -0.08322 0.79410
Hazard Ratio 1 2 1.427000 0.92010 2.21300
Anxiety and depression combined --- Yes:No 1 2 0.637800 0.19940 0.24710 1.02900
Hazard Ratio 1 2 1.892000 1.28000 2.79700
Maternal morbidity --- Yes:No 1 2 -0.007480 0.37660 -0.74570 0.73070
Hazard Ratio 1 2 0.992500 0.47440 2.07700
Wald Statistics for Surv(days.to.event, outcome.bin)
χ2 d.f. P
MOUD receipt timing 0.48 2 0.7870
Total days supplied MOUD (method 3) 2.14 1 0.1432
Year of delivery 17.64 1 <0.0001
Age at delivery 1.44 1 0.2302
Route of delivery 0.00 1 0.9652
Number of Gestation weeks 0.92 1 0.3385
Combined pain 1.39 1 0.2380
Alcohol or other substance use 3.15 1 0.0757
Benzodiazepine or anticonvulsant use 2.52 1 0.1121
Anxiety and depression combined 10.23 1 0.0014
Maternal morbidity 0.00 1 0.9841
TOTAL 64.13 12 <0.0001


Timing only

Effects   Response: Surv(days.to.event, outcome.bin)
Low High Δ Effect S.E. Lower 0.95 Upper 0.95
Year of delivery 2016 2018 2 0.40600 0.09581 0.218300 0.59380
Hazard Ratio 2016 2018 2 1.50100 1.244000 1.81100
Age at delivery 27 31 4 -0.10250 0.08031 -0.259900 0.05489
Hazard Ratio 27 31 4 0.90260 0.771100 1.05600
Number of Gestation weeks 39 37 -2 0.07466 0.07228 -0.067000 0.21630
Hazard Ratio 39 37 -2 1.07800 0.935200 1.24200
MOUD receipt timing --- Only pre:Both pre and post 3 1 0.47820 0.23970 0.008477 0.94790
Hazard Ratio 3 1 1.61300 1.009000 2.58000
MOUD receipt timing --- Only post:Both pre and post 3 2 0.55420 0.25520 0.054010 1.05400
Hazard Ratio 3 2 1.74100 1.055000 2.87000
Route of delivery --- Cesarean:Vaginal 2 1 -0.02199 0.19260 -0.399500 0.35560
Hazard Ratio 2 1 0.97830 0.670600 1.42700
Combined pain --- No:Yes 2 1 0.23320 0.19820 -0.155300 0.62160
Hazard Ratio 2 1 1.26300 0.856200 1.86200
Alcohol or other substance use --- Yes:No 1 2 0.35440 0.18430 -0.006726 0.71560
Hazard Ratio 1 2 1.42500 0.993300 2.04500
Benzodiazepine or anticonvulsant use --- Yes:No 1 2 0.35410 0.22380 -0.084660 0.79280
Hazard Ratio 1 2 1.42500 0.918800 2.21000
Anxiety and depression combined --- Yes:No 1 2 0.63990 0.19910 0.249800 1.03000
Hazard Ratio 1 2 1.89600 1.284000 2.80100
Maternal morbidity --- Yes:No 1 2 -0.01368 0.37620 -0.751000 0.72370
Hazard Ratio 1 2 0.98640 0.471900 2.06200
Wald Statistics for Surv(days.to.event, outcome.bin)
χ2 d.f. P
MOUD receipt timing 7.27 2 0.0264
Year of delivery 17.94 1 <0.0001
Age at delivery 1.63 1 0.2013
Route of delivery 0.01 1 0.9092
Number of Gestation weeks 1.07 1 0.3010
Combined pain 1.38 1 0.2394
Alcohol or other substance use 3.70 1 0.0544
Benzodiazepine or anticonvulsant use 2.50 1 0.1136
Anxiety and depression combined 10.33 1 0.0013
Maternal morbidity 0.00 1 0.9710
TOTAL 61.12 11 <0.0001


Linear continuous terms (timing + days BUP)

Effects   Response: Surv(days.to.event, outcome.bin)
Low High Δ Effect S.E. Lower 0.95 Upper 0.95
Total days supplied buprenorphine 1 31 30 -0.17740 0.10010 -0.37370 0.01879
Hazard Ratio 1 31 30 0.83740 0.68820 1.01900
Year of delivery 2014 2018 4 0.81690 0.19360 0.43750 1.19600
Hazard Ratio 2014 2018 4 2.26300 1.54900 3.30800
Age at delivery 25 35 10 -0.21850 0.19860 -0.60770 0.17070
Hazard Ratio 25 35 10 0.80370 0.54460 1.18600
Number of Gestation weeks 37 39 2 -0.06631 0.07196 -0.20740 0.07473
Hazard Ratio 37 39 2 0.93580 0.81270 1.07800
MOUD receipt timing --- Only pre:Both pre and post 3 1 0.17510 0.32130 -0.45470 0.80500
Hazard Ratio 3 1 1.19100 0.63470 2.23700
MOUD receipt timing --- Only post:Both pre and post 3 2 0.34510 0.35100 -0.34290 1.03300
Hazard Ratio 3 2 1.41200 0.70970 2.81000
Route of delivery --- Cesarean:Vaginal 2 1 -0.05573 0.19610 -0.44000 0.32860
Hazard Ratio 2 1 0.94580 0.64400 1.38900
Combined pain --- No:Yes 2 1 0.23430 0.19910 -0.15600 0.62460
Hazard Ratio 2 1 1.26400 0.85550 1.86800
Alcohol or other substance use --- Yes:No 1 2 0.40080 0.18590 0.03634 0.76530
Hazard Ratio 1 2 1.49300 1.03700 2.15000
Benzodiazepine or anticonvulsant use --- Yes:No 1 2 0.36230 0.22480 -0.07839 0.80300
Hazard Ratio 1 2 1.43700 0.92460 2.23200
Anxiety and depression combined --- Yes:No 1 2 0.65390 0.20040 0.26120 1.04700
Hazard Ratio 1 2 1.92300 1.29800 2.84800
Maternal morbidity --- Yes:No 1 2 -0.02123 0.37770 -0.76150 0.71910
Hazard Ratio 1 2 0.97900 0.46690 2.05300
Wald Statistics for Surv(days.to.event, outcome.bin)
χ2 d.f. P
MOUD receipt timing 0.97 2 0.6157
Total days supplied buprenorphine 3.14 1 0.0763
Year of delivery 17.78 1 <0.0001
Age at delivery 1.21 1 0.2709
Route of delivery 0.08 1 0.7764
Number of Gestation weeks 0.85 1 0.3561
Combined pain 1.38 1 0.2395
Alcohol or other substance use 4.65 1 0.0311
Benzodiazepine or anticonvulsant use 2.60 1 0.1070
Anxiety and depression combined 10.64 1 0.0011
Maternal morbidity 0.00 1 0.9551
TOTAL 70.28 12 <0.0001


Timing only BUP

Effects   Response: Surv(days.to.event, outcome.bin)
Low High Δ Effect S.E. Lower 0.95 Upper 0.95
Year of delivery 2014 2018 4 0.81930 0.19160 0.44380 1.19500
Hazard Ratio 2014 2018 4 2.26900 1.55900 3.30300
Age at delivery 25 35 10 -0.24100 0.20120 -0.63530 0.15330
Hazard Ratio 25 35 10 0.78590 0.52980 1.16600
Number of Gestation weeks 37 39 2 -0.07246 0.07101 -0.21160 0.06673
Hazard Ratio 37 39 2 0.93010 0.80930 1.06900
MOUD receipt timing --- Only pre:Both pre and post 3 1 0.52130 0.24070 0.04942 0.99310
Hazard Ratio 3 1 1.68400 1.05100 2.70000
MOUD receipt timing --- Only post:Both pre and post 3 2 0.77540 0.25690 0.27180 1.27900
Hazard Ratio 3 2 2.17200 1.31200 3.59300
Route of delivery --- Cesarean:Vaginal 2 1 -0.07435 0.19530 -0.45710 0.30840
Hazard Ratio 2 1 0.92830 0.63310 1.36100
Combined pain --- No:Yes 2 1 0.23410 0.19920 -0.15640 0.62460
Hazard Ratio 2 1 1.26400 0.85520 1.86800
Alcohol or other substance use --- Yes:No 1 2 0.43350 0.18580 0.06937 0.79770
Hazard Ratio 1 2 1.54300 1.07200 2.22000
Benzodiazepine or anticonvulsant use --- Yes:No 1 2 0.36170 0.22480 -0.07900 0.80230
Hazard Ratio 1 2 1.43600 0.92400 2.23100
Anxiety and depression combined --- Yes:No 1 2 0.65680 0.20000 0.26490 1.04900
Hazard Ratio 1 2 1.92900 1.30300 2.85400
Maternal morbidity --- Yes:No 1 2 -0.02996 0.37720 -0.76920 0.70930
Hazard Ratio 1 2 0.97050 0.46340 2.03300
Wald Statistics for Surv(days.to.event, outcome.bin)
χ2 d.f. P
MOUD receipt timing 11.65 2 0.0029
Year of delivery 18.27 1 <0.0001
Age at delivery 1.44 1 0.2307
Route of delivery 0.14 1 0.7035
Number of Gestation weeks 1.04 1 0.3068
Combined pain 1.38 1 0.2402
Alcohol or other substance use 5.45 1 0.0196
Benzodiazepine or anticonvulsant use 2.59 1 0.1076
Anxiety and depression combined 10.78 1 0.0010
Maternal morbidity 0.01 1 0.9366
TOTAL 67.10 11 <0.0001


8 Sensitivity analysis 2007-2018

8.1 Descriptive Statistics

  • There are 5728 pregnancies in 5049 unique individuals
    N Overall
    (N=5728)
    Year of delivery 5728 (100.00)
            Median (interquartile range) 2015 (2014—2017)
            Range 2007—2018
    Age at delivery 5728 (100.00)
            Median (interquartile range) 27 (24—30)
            Range 17—44
    Number of Gestation weeks 5728 (100.00)
            Median (interquartile range) 39 (37—39)
            Range 21—42
    Race 5728 (100.00)
            American Indian or Alaska Native     18/5728 (0.31)
            Asian or Pacific Islander         8/5728 (0.14)
            Black of African American     140/5728 (2.44)
            Other or Unknown     41/5728 (0.72)
            White 5521/5728 (96.39)
    Hispanic : Not Hispanic 5721 (99.88) 5675/5721 (99.20)
    Race/Ethnicity combined 5728 (100.00)
            Hispanic     46/5728 (0.80)
            Non-Hispanic Asian         8/5728 (0.14)
            Non-Hispanic Black     139/5728 (2.43)
            Non-Hispanic Other     45/5728 (0.79)
            Non-Hispanic White 5490/5728 (95.84)
    Route of delivery : Vaginal 5728 (100.00) 3744/5728 (65.36)
    Number of previous pregnancies 5596 (97.70)
            Median (interquartile range) 2 (1—3)
            Range 0—23
    Final outcome 5728 (100.00)
            Death     20/5728 (0.35)
            Overdose     56/5728 (0.98)
            Loss of enrollment     671/5728 (11.71)
            Censored 4981/5728 (86.96)
    Final outcome (w/o all payer data) 5728 (100.00)
            Death         8/5728 (0.14)
            Overdose     51/5728 (0.89)
            Loss of enrollment     688/5728 (12.01)
            Censored 4981/5728 (86.96)
    Total days supplied MOUD 5728 (100.00)
            Median (interquartile range) 93 (56—120)
            Range 1—132
    Total days supplied MOUD before delivery 5728 (100.00)
            Median (interquartile range) 74 (36—90)
            Range 0—90
    Total days supplied MOUD after delivery 5728 (100.00)
            Median (interquartile range) 29 (7—41)
            Range 0—42
    Total days supplied MOUD (method 2) 5728 (100.00)
            Median (interquartile range) 98 (56—122)
            Range 1—132
    Total days supplied MOUD before delivery (method 2) 5728 (100.00)
            Median (interquartile range) 74 (36—90)
            Range 0—90
    Total days supplied MOUD after delivery (method 2) 5728 (100.00)
            Median (interquartile range) 30 (12—42)
            Range 0—42
    Total days supplied MOUD (method 3) 5728 (100.00)
            Median (interquartile range) 88 (49—110)
            Range 1—132
    Total days supplied MOUD before delivery (method 3) 5728 (100.00)
            Median (interquartile range) 62 (30—77)
            Range 0—90
    Total days supplied MOUD after delivery (method 3) 5728 (100.00)
            Median (interquartile range) 30 (13—40)
            Range 0—42
    Avg dose pre-delivery (mg) 5669 (98.97)
            Median (interquartile range) 14.55 (8.00—16.00)
            Range 0.00—50.00
    Avg dose post-delivery (mg) 5669 (98.97)
            Median (interquartile range) 9.21 (4.00—16.00)
            Range 0.00—53.57
    Avg dose exposure (mg) 5669 (98.97)
            Median (interquartile range) 14.22 (9.94—16.00)
            Range 0.14—53.57
    Total days buprenorphine before delivery (method 3) 5621 (98.13)
            Median (interquartile range) 62.00 (30.00—77.00)
            Range 0.00—90.00
    Total days buprenorphine after delivery (method 3) 5621 (98.13)
            Median (interquartile range) 30.00 (13.00—40.00)
            Range 0.00—42.00
    Total days supplied buprenorphine 5621 (98.13)
            Median (interquartile range) 89.00 (50.00—111.00)
            Range 1.00—132.00
    Avg dose BUP pre-delivery (mg) 5621 (98.13)
            Median (interquartile range) 14.49 (8.00—16.00)
            Range 0.00—35.42
    Avg dose BUP post-delivery (mg) 5621 (98.13)
            Median (interquartile range) 9.14 (4.00—16.00)
            Range 0.00—42.67
    Avg dose BUP exposure (mg) 5621 (98.13)
            Median (interquartile range) 14.15 (9.79—16.00)
            Range 0.14—42.67
    Combined pain : Yes 5728 (100.00) 4537/5728 (79.21)
    Schizophrenia or personality disorder : Yes 5728 (100.00)     426/5728 (7.44)
    Alcohol or other substance use : Yes 5728 (100.00) 2704/5728 (47.21)
    Benzodiazepine or anticonvulsant use : Yes 5728 (100.00)     906/5728 (15.82)
    Maternal morbidity : Yes 5728 (100.00)     470/5728 (8.21)
    Anxiety and depression combined : Yes 5728 (100.00) 2542/5728 (44.38)
    Back pain : Yes 5728 (100.00) 2388/5728 (41.69)
    Depression : Yes 5728 (100.00) 2173/5728 (37.94)
    Bipolar disorder : Yes 5728 (100.00)     618/5728 (10.79)
    Other substance use : Yes 5728 (100.00) 2582/5728 (45.08)
    Tobacco use : Yes 5728 (100.00) 4105/5728 (71.67)
    Med NSAIDS : Yes 5728 (100.00) 3468/5728 (60.54)
    Schizophrenia psychotic disorders : Yes 5728 (100.00)     318/5728 (5.55)
    Anxiety : Yes 5728 (100.00) 1048/5728 (18.30)
    Med benzodiazepine use : Yes 5728 (100.00)     599/5728 (10.46)
    Maternal morbidity : Yes 5728 (100.00)     470/5728 (8.21)
    Dental pain : Yes 5728 (100.00)     229/5728 (4.00)
    Alcohol use disorder : Yes 5728 (100.00)     410/5728 (7.16)
    Med anticonvulsant use : Yes 5728 (100.00)     367/5728 (6.41)
    Med muscle relaxant use : Yes 5728 (100.00)     280/5728 (4.89)
    Personality disorder : Yes 5728 (100.00)     183/5728 (3.19)
    Fibromyalgia : Yes 5728 (100.00)     303/5728 (5.29)
    CDC SVI overall percentile ranking of all 4 themes 5363 (93.63)
            Median (interquartile range) 0.57 (0.36—0.79)
            Range 0.00—1.00
    N is the number of non-missing value. 1Kruskal-Wallis. 2Pearson. 3Wilcoxon.

8.1.1 Time to event for overdose and death

Descriptives deathod18$days.to.event
image
nmissingdistinctInfoMeanpMedianGmd.05.10.25.50.75.90.95
760721187.1190106.9 18.75 46.00123.75210.50268.50299.50308.50
lowest : 2 7 8 18 19 , highest: 304 308 310 316 319 Descriptives death18$days.to.event
image
nmissingdistinctInfoMeanpMedianGmd.05.10.25.50.75.90.95
200201165.2163.5118.4 18.15 33.40 58.75174.50262.50280.10290.90
 Value         2   19   35   45   52   61  128  140  156  171  178  181  217  240
 Frequency     1    1    1    1    1    1    1    1    1    1    1    1    1    1
 Proportion 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05
                                         
 Value       261  267  275  279  290  308
 Frequency     1    1    1    1    1    1
 Proportion 0.05 0.05 0.05 0.05 0.05 0.05 
For the frequency table, variable is rounded to the nearest 0 Descriptives od18$days.to.event
image
nmissingdistinctInfoMeanpMedianGmd.05.10.25.50.75.90.95
560541195199.8103 24.75 64.50129.50216.00270.25301.50310.00
lowest : 7 8 18 27 47 , highest: 302 304 310 316 319


Survival Analysis

8.2 Kaplan Meier Plot

Call: survfit(formula = Surv(days.to.event, outcome.bin) ~ 1, data = moud18)

        n events median 0.95LCL 0.95UCL
[1,] 5728     76     NA      NA      NA

   Min. 1st Qu.  Median    Mean 3rd Qu.    Max. 
    2.0   120.0   208.0   186.9   270.0   323.0 
time probability
2 0.9998254
7 0.9996508
8 0.9994763
18 0.9993017
19 0.9991271
27 0.9989525
35 0.9987779
45 0.9986034
47 0.9984288
52 0.9982542
61 0.9980796
63 0.9979050
66 0.9977304
69 0.9975559
97 0.9973813
110 0.9972067
111 0.9970321
112 0.9968575
120 0.9966830
125 0.9965084
128 0.9963338
131 0.9961592
138 0.9958101
140 0.9956355
144 0.9954609
147 0.9952863
156 0.9951117
166 0.9949372
171 0.9947626
175 0.9945880
177 0.9944134
178 0.9942388
181 0.9940642
182 0.9938897
184 0.9937151
188 0.9935405
208 0.9933659
213 0.9931913
215 0.9930168
217 0.9926676
220 0.9924930
222 0.9923184
223 0.9921439
228 0.9919693
229 0.9917947
235 0.9916201
239 0.9914455
240 0.9910964
246 0.9909218
258 0.9907472
261 0.9905726
265 0.9903980
267 0.9902235
268 0.9900489
270 0.9898743
271 0.9896997
274 0.9895251
275 0.9893506
279 0.9891760
287 0.9890014
289 0.9888268
290 0.9886522
295 0.9884777
296 0.9883031
298 0.9881285
301 0.9879539
302 0.9877793
304 0.9876047
308 0.9874302
310 0.9870810
316 0.9869064
319 0.9867318
323 0.9867318

Multivariable Cox PH model

8.2.1 Linear continuous terms

Effects   Response: Surv(days.to.event, outcome.bin)
Low High Δ Effect S.E. Lower 0.95 Upper 0.95
Year of delivery 2016 2018 2 0.32390 0.15410 0.02183 0.6260
Hazard Ratio 2016 2018 2 1.38300 1.02200 1.8700
Total days supplied MOUD (method 3) 1 31 30 -0.26840 0.08350 -0.43200 -0.1047
Hazard Ratio 1 31 30 0.76460 0.64920 0.9006
Age at delivery 27 31 4 -0.04082 0.10860 -0.25370 0.1721
Hazard Ratio 27 31 4 0.96000 0.77590 1.1880
Number of Gestation weeks 39 37 -2 0.09981 0.09263 -0.08174 0.2814
Hazard Ratio 39 37 -2 1.10500 0.92150 1.3250
Route of delivery --- Cesarean:Vaginal 2 1 0.18350 0.24580 -0.29820 0.6652
Hazard Ratio 2 1 1.20100 0.74220 1.9450
Combined pain --- No:Yes 2 1 0.26780 0.27150 -0.26430 0.8000
Hazard Ratio 2 1 1.30700 0.76780 2.2250
Alcohol or other substance use --- Yes:No 1 2 0.06777 0.23750 -0.39760 0.5332
Hazard Ratio 1 2 1.07000 0.67190 1.7040
Benzodiazepine or anticonvulsant use --- Yes:No 1 2 0.22720 0.28610 -0.33350 0.7879
Hazard Ratio 1 2 1.25500 0.71640 2.1990
Anxiety and depression combined --- Yes:No 1 2 0.74930 0.25280 0.25380 1.2450
Hazard Ratio 1 2 2.11600 1.28900 3.4720
Maternal morbidity --- Yes:No 1 2 -0.15200 0.46710 -1.06800 0.7636
Hazard Ratio 1 2 0.85900 0.34380 2.1460
Wald Statistics for Surv(days.to.event, outcome.bin)
χ2 d.f. P
Year of delivery 4.41 1 0.0358
Total days supplied MOUD (method 3) 10.33 1 0.0013
Age at delivery 0.14 1 0.7069
Route of delivery 0.56 1 0.4553
Number of Gestation weeks 1.16 1 0.2809
Combined pain 0.97 1 0.3239
Alcohol or other substance use 0.08 1 0.7752
Benzodiazepine or anticonvulsant use 0.63 1 0.4268
Anxiety and depression combined 8.78 1 0.0030
Maternal morbidity 0.11 1 0.7449
TOTAL 39.60 10 <0.0001

`


8.2.2 Univariable HR

Effects   Response: Surv(days.to.event, outcome.bin)
Low High Δ Effect S.E. Lower 0.95 Upper 0.95
Total days supplied MOUD (method 3) 1 31 30 -0.293 0.08475 -0.4591 -0.1269
Hazard Ratio 1 31 30 0.746 0.6318 0.8808
Wald Statistics for Surv(days.to.event, outcome.bin)
χ2 d.f. P
Total days supplied MOUD (method 3) 11.95 1 0.0005
TOTAL 11.95 1 0.0005

9 Sensitivity analysis shift-forward

N Overall
(N=7472)
Total days supplied MOUD (method 3) 7472 (100.00)
        Median (interquartile range) 89 (47—112)
        Range 1—132
MOUD days exposure shifted approach 7472 (100.00)
        Median (interquartile range) 92 (50—115)
        Range 1—132
N is the number of non-missing value. 1Kruskal-Wallis. 2Pearson. 3Wilcoxon.

9.1 Survival Analysis

Multivariable Cox PH model

Linear continuous terms

Effects   Response: Surv(days.to.event, outcome.bin)
Low High Δ Effect S.E. Lower 0.95 Upper 0.95
Year of delivery 2016 2018 2 0.407700 0.09674 0.21810 0.59740
Hazard Ratio 2016 2018 2 1.503000 1.24400 1.81700
MOUD days exposure shifted approach 1 31 30 -0.181000 0.06375 -0.30600 -0.05608
Hazard Ratio 1 31 30 0.834400 0.73640 0.94550
Age at delivery 27 31 4 -0.092560 0.07950 -0.24840 0.06326
Hazard Ratio 27 31 4 0.911600 0.78010 1.06500
Number of Gestation weeks 39 37 -2 0.072490 0.07386 -0.07227 0.21720
Hazard Ratio 39 37 -2 1.075000 0.93030 1.24300
Route of delivery --- Cesarean:Vaginal 2 1 -0.007594 0.19320 -0.38620 0.37100
Hazard Ratio 2 1 0.992400 0.67960 1.44900
Combined pain --- No:Yes 2 1 0.233600 0.19800 -0.15430 0.62160
Hazard Ratio 2 1 1.263000 0.85700 1.86200
Alcohol or other substance use --- Yes:No 1 2 0.331500 0.18540 -0.03190 0.69490
Hazard Ratio 1 2 1.393000 0.96860 2.00400
Benzodiazepine or anticonvulsant use --- Yes:No 1 2 0.354000 0.22390 -0.08485 0.79290
Hazard Ratio 1 2 1.425000 0.91870 2.21000
Anxiety and depression combined --- Yes:No 1 2 0.637700 0.20080 0.24420 1.03100
Hazard Ratio 1 2 1.892000 1.27700 2.80500
Maternal morbidity --- Yes:No 1 2 -0.001804 0.37690 -0.74050 0.73690
Hazard Ratio 1 2 0.998200 0.47690 2.08900
Wald Statistics for Surv(days.to.event, outcome.bin)
χ2 d.f. P
Year of delivery 17.74 1 <0.0001
MOUD days exposure shifted approach 8.06 1 0.0045
Age at delivery 1.36 1 0.2439
Route of delivery 0.00 1 0.9687
Number of Gestation weeks 0.97 1 0.3259
Combined pain 1.39 1 0.2380
Alcohol or other substance use 3.20 1 0.0738
Benzodiazepine or anticonvulsant use 2.50 1 0.1137
Anxiety and depression combined 10.08 1 0.0015
Maternal morbidity 0.00 1 0.9962
TOTAL 61.20 10 <0.0001

9.1.1 Univariable HR

Effects   Response: Surv(days.to.event, outcome.bin)
Low High Δ Effect S.E. Lower 0.95 Upper 0.95
MOUD days exposure shifted approach 1 31 30 -0.2115 0.06532 -0.3395 -0.08345
Hazard Ratio 1 31 30 0.8094 0.7121 0.91990
Wald Statistics for Surv(days.to.event, outcome.bin)
χ2 d.f. P
MOUD days exposure shifted approach 10.47 1 0.0012
TOTAL 10.47 1 0.0012

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